Susan Schenk

Susan Schenk
University of Otago · Department of Zoology

PhD

About

126
Publications
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Publications

Publications (126)
Article
MDMA is a non-selective monoamine releasing stimulant with potent serotonergic effects - a pharmacological effect not typically associated with drugs of misuse or efficacious reinforcers. Nonetheless, MDMA is misused by humans and self-administered by laboratory animals. We have previously shown that repeated exposure to MDMA sensitized both the lo...
Article
Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases in synaptic dopamine (DA). The ratio of drug‐stimulated increases in synaptic DA, relative to 5HT, predicts the abuse liability; drugs with higher DA:5HT ratios are more likely to be...
Article
Full-text available
Background People who suffer from opioid use disorders (illicit and prescription opioids) are disproportionately involved in criminal activities and a high percentage of those incarcerated suffer from these disorders. Despite the established efficacy of pharmacotherapy for opioid use disorders this intervention is infrequently offered to criminal j...
Article
Cognitive flexibility refers to the mental processes that allow us to adapt our behaviour as environmental circumstances change. In this paper, we describe various procedures that are commonly used to measure cognitive flexibility in humans. We then provide evidence of a relationship between cognitive inflexibility and various psychiatric disorders...
Article
Repeated exposure to drugs produces a plethora of persistent brain changes, some of which underlie the development of drug addiction. An important objective of addiction research is to identify the brain changes that might mediate the transition from drug use to drug misuse. The persistent accumulation of the transcription factor, ∆FosB, following...
Article
Full-text available
Rationale3,4-Methylenedioxymethamphetamine (MDMA) preferentially increases synaptic serotonin (5HT). This response was attenuated following repeated exposure but there was recovery as a result of abstinence. Effects of abstinence on self-administration of many drugs have been documented but the impact on MDMA self-administration is unknown. Objecti...
Article
Background: For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via pros...
Article
Most studies on discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) have been conducted using a relatively low dose (1.5 mg/kg), and those studies have invariably implicated serotonergic mechanisms. In contrast, dopaminergic mechanisms mediate the discriminative stimulus effects of amphetamine (AMPH). Some studies have sugge...
Article
Full-text available
RationaleRepeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown. Objectives This study determined the effect of a sensitizing regimen of MDMA expo...
Article
Studies that have attributed the discriminative stimulus effects of ±3,4-methylenedioxymethamphetamine (MDMA) to serotonergic mechanisms typically use a relatively low training dose of 1.5 mg/kg. The role of serotonin in the discriminative stimulus effects of higher doses of MDMA is, however, unknown. Separate groups of rats were trained to discrim...
Article
Acute exposure to ± 3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5-HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measure...
Article
Full-text available
Rationale 3,4 Methylenedioxymethamphetamine (MDMA) preferentially stimulates the release of serotonin (5-HT) that subsequently produces behavioral responses by activation of post-synaptic receptor mechanisms. The 5-HT1A and 5-HT1B receptors are both well localized to regulate dopamine (DA) release, and have been implicated in modulating the reinfor...
Article
Full-text available
Rationale Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT1A and 5-HT1B recept...
Article
Background. Studies of the discriminative stimulus effects of the recreational drug, ±3,4-methylenedioxymethamphetamine (MDMA), typically use a dose of 1.5 mg/kg during training. This dose is relatively low compared to those used in other behavioral paradigms. Purpose. The present study assessed the ability of this low dose of MDMA and a higher dos...
Article
As is the case with other drugs of abuse, a proportion of ecstasy users develop symptoms consistent with a substance use disorder (SUD). In this paper, we propose that the pharmacology of MDMA, the primary psychoactive component of ecstasy tablets, changes markedly with repeated exposure and that neuroadaptations in dopamine and serotonin brain sys...
Article
Almost every neurological disease directly or indirectly affects synapse function in the brain. However, these diseases alter synapses through different mechanisms, ultimately resulting in altered synaptic transmission and/or plasticity. Glutamate is the major neurotransmitter that mediates excitatory synaptic transmission in the brain through acti...
Article
Effects of MDMA exposure on MDMA-produced hyperactivity is dependent on the exposure regimen; high-dose exposure produced tolerance whereas repeated, intermittent exposure produced sensitized responses. In the present study we measured the impact of MDMA self-administration on MDMA-produced hyperactivity. Rats self-administered a total of 165 mg/kg...
Article
Drug discrimination studies have suggested that the subjective effects of low doses of (+/-)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have pri...
Conference Paper
Drug addiction places a tremendous financial and psychological burden on society, families and the individual. Interestingly, only a small percentage of individuals who use drugs of abuse develop addictive behaviours. Clinical studies have shown that there is a subset of the population that has a genetically determined reduction in the serotonin tr...
Article
The current study aimed to elucidate the role of pharmacokinetic (PK) parameters and neurotransmitter efflux in explaining variability in (±) 3, 4-methylenedioxymethamphetamine (MDMA) self-administration in rats. PK profiles of MDMA and its major metabolites were determined after the administration of 1.0 mg/kg MDMA (iv) prior to, and following, th...
Article
Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
Article
A consistent effect of repeated exposure to 3,4 methylenedioxymethamphetamine (MDMA) is a decrease in the tissue levels of serotonin (5-HT). A variety of behavioural and neurochemical tests were conducted to determine whether the tissue deficits were accompanied by an increased sensitivity of the 5-HT(1a) autoreceptor. Tests were conducted 2 weeks...
Article
It has been suggested that the response to novelty and impulsivity predict the latency to acquisition and maintenance of drug self-administration, respectively. The aim of this study was to examine the relationship between these two traits and (1) the latency to acquisition and (2) maintenance (drug-seeking) of 3,4-methylenedioxymethamphetamine (MD...
Article
Acute exposure to (±) 3, 4-methylenedioxymethamphetamine (MDMA) produces hyperlocomotion that is preferentially expressed in the periphery of closed chambers. Following repeated administration, however, a sensitized hyperlocomotor response is preferentially expressed in the center of an activity box, so that the response resembles the more generali...
Article
Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse side-effects such as sedation, dysphoria, and depression limit their therapeutic use. Recently, salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaine-induced drug seeking in a model of relapse in rats. The present s...
Article
The present study provides a profile of acqui- sition and maintenance of self-administration of +/-3,4- methylenedioxymethamphetamine (MDMA) obtained from a large cohort of rats tested during a 2 year period. Of the 128 rats, 49% self-administered 1.0 mg/kg/infusion MDMA to an initial criterion within a 25 day cut-off period. The number of test ses...
Article
3,4-Methylenedioxymethamphetamine (MDMA) use and abuse have been increasing worldwide. Of concern, exposure to high doses of MDMA decreases several markers of serotonin (5HT) neurotransmission and produces deficits in tissue levels of 5HT. Studies in laboratory animals have been conducted primarily following large doses (20.0-80.0 mg/kg) of experim...
Article
Full-text available
IDARS is an acronym for the International Drug Abuse Research Society. Apart from our scientific and educational purposes, we communicate information to the general and scientific community about substance abuse and addiction science and treatment potential. Members of IDARS are research scientists and clinicians from around the world, with schedul...
Article
It has been suggested that dopaminergic mechanisms mediate relapse to drug-seeking behavior and both D1- and D2-like receptor mechanisms have been implicated. In contrast to self-administration of other drugs, there is a relative paucity of studies that has examined the pharmacological basis of methamphetamine (MA) seeking. Accordingly, the present...
Article
The present study was undertaken to examine effects of self-administered MDMA on novel object exploration (NOR) memory. Self-administration was conducted during daily 2 h tests that continued until a total of 165 mg/kg was self-administered (range = 13-41 days for individual rats). Control rats were placed in the self-administration boxes during da...
Article
A number of reviews have focused on the short- and long-term effects of MDMA and, in particular, on the persistent deficits in serotonin neurotransmission that accompany some exposure regimens. The mechanisms underlying the serotonin deficits and their relevance to various behavioral and cognitive consequences of MDMA use are still being debated. I...
Article
Animal models of drug-seeking suggest that exposure to cues associated with self-administered drugs and drug primes might precipitate relapse via activation of central dopaminergic substrates. The effects of priming injections of dopamine and 5-HT agonists on drug-seeking and effects of dopamine antagonists on methylenedioxymethamphetamine (MDMA)-p...
Article
Tolerance to the behavioural effects of 3,4-methylenedioxymethamphetamine (MDMA) following high dose exposure has been attributed to alterations in serotonergic systems. The present study aimed to determine whether decreased 5-HT release and/or 5-HT(2A/C) receptor desensitization might play a role in tolerance by measuring the response to selective...
Article
Full-text available
3,4-methylenedioxymethamphetamine (MDMA) causes long-term serotonin depletion and reduced serotonin transporter (SERT) function in humans and in animal models. Using quantitative Western blotting and real-time PCR, we have shown that total SERT protein in the striatum and nucleus accumbens and mRNA levels in the dorsal raphe nucleus were not signif...
Article
In laboratory animals, exposure to priming injections of 3,4-methylenedioxymethamphetamine (MDMA) produced drug seeking following extinction of MDMA self-administration. This study aimed to evaluate whether the magnitude of drug seeking was related to latency to acquisition of MDMA self-administration and increases in striatal dopamine, as measured...
Article
A number of studies have shown that exposure to high doses of methamphetamine (MA) is toxic to central dopamine (DA) and serotonin (5-HT) neurons. In most of those studies, however, high doses of MA were experimenter-administered during a short exposure time. Because contingency is a determinant for many effects of drug exposure, the present object...
Article
The prevalence of 3,4-methylenedioxymethamphetamine (MDMA) use has increased globally and the pattern of consumption has changed considerably. Previously, a subculture of MDMA users was fairly restricted to the dance club scene. More recently, use has spread outside of this subculture and now many users consume MDMA frequently and in large amounts...
Article
It has been suggested that activation of dopamine D1-like and D2-like receptors contribute equally to the maintenance of drug self-administration. This study compared the contribution of these receptor subtypes to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (MA) self-administration. Effects of pretreatment with the D2-like receptor...
Article
Our previous work indicated that pretreatment with the selective kappa-opioid receptor (KOPr) agonist, U69593, attenuated the ability of priming injections of cocaine to reinstate extinguished cocaine-seeking behavior. The present study expanded these initial tests to include other traditional KOPr agonists, U50488H, spiradoline (SPR), and salvinor...
Article
The behavioral profile in response to (+/-)-3,4-methylenedioxymethamphetamine (MDMA) is characterized by acute hyperlocomotion that is primarily restricted to the periphery of the open field, whereas behavioral sensitization to MDMA reflects a selective increase in activity in the central zone, suggesting that acute effects and sensitization might...
Article
Exposure to self-administered drugs is sufficient to produce drug-seeking in animal models. In many cases priming injections of drugs that share discriminative stimulus properties with the self-administered drug also can lead to drug-seeking, suggesting that exposure might precipitate relapse. The present investigation examined the ability of MDMA...
Article
Full-text available
Factors that increase an individual's susceptibility to cocaine dependence remain largely unknown. We have previously shown that adult outbred male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their locomotor activity following the administration of a single dose of cocaine (10...
Article
3,4-Methylenedioxymethamphetamine (MDMA) self-administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug-naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self-admi...
Article
The ability of benzylpiperazine (BZP) to substitute for cocaine and to initiate self-administration in drug-naive subjects was assessed to determine whether BZP has abuse liability. Further, the effects of a pretreatment with dopamine D1-like receptor antagonist (SCH23390) were examined to elucidate the mechanisms associated with BZP reward. First,...
Article
Full-text available
N-benzylpiperazine (BZP) is the active ingredient in recreational 'party' or 'p.e.p.' pills, which are used to provide a stimulant, euphoric effect akin to that of methylenedioxymethamphetamine (MDMA, 'ecstasy'). BZP predominantly affects dopamine neurotransmission in a similar fashion to known 'drugs of abuse', such as methamphetamine and cocaine,...
Article
Like other psychostimulant drugs, acute exposure to benzylpiperazine (BZP) increases dopaminergic neurotransmission, producing hyperactivity and stereotypy. The consequences of repeated BZP exposure have not however been investigated. The effects of acute and repeated BZP and methamphetamine (MA) exposure on locomotor activity and stereotypy were m...
Article
Several studies suggest that a dopamine transporter uptake inhibitor that has a slower onset and longer duration of action than cocaine in animal behavioral measures and decreases cocaine self-administration would be useful as an indirect dopamine agonist pharmacotherapy to treat cocaine addiction. In the present study, we compared five 3-phenyltro...
Article
There has been some controversy in the literature concerning the ability of +/-3,4 methylenedioxymethamphetamine (MDMA) to reinforce operant responding in rats. In the present study, operant responding maintained by intravenous MDMA infusions increased when the fixed ratio schedule was increased from 1 to 5, decreased when saline was substituted fo...
Article
This study investigated the relationship between positive and negative subjective responses at the time of initial cocaine use with adult cocaine dependence and life-time use rates. Psychostimulant pre-exposure, regular smoking or stimulant treatment before initiation were examined to explore the incentive sensitization theory of addiction. A total...
Article
Recent evidence suggests that the disruptive effects of acute exposure to (+/-)3,4-methylene dioxymethamphetamine (MDMA) on memory performance may be the result of increased confusion between previous-trial and current-trial events. The current study tested this hypothesis by examining the effects of MDMA on performance of rats in a delayed matchin...
Article
3,4-methylenedioxymethamphetamine (MDMA) exposure was reported to result in deficits in serotonergic neurotransmission with concomitant behavioral suppression and tolerance to MDMA. Some data have also suggested that the neurochemical deficits recover over time, raising the question as to whether behavioral suppression would show a similar recovery...
Article
This study compared the effects of (+/-)3,4-methylenedioxymethamphetamine, d-amphetamine, and cocaine on performance of rats in a delayed matching-to-sample procedure using a variety of indices of performance to determine the mechanism by which working memory task impairments arise. All 3 drugs produced an overall delay-independent decrease in accu...
Article
Recently, we demonstrated that (+/-)-3,4-methylenedioxymethamphetamine (MDMA; ecstasy) was reliably and dose-dependently self-administered by previously drug-naïve laboratory rats. The neurochemical basis of MDMA self-administration has not, however, been extensively studied. The present study investigated the role of dopamine in MDMA self-administ...
Article
+/-3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") use is increasing around the globe but there is a paucity of studies examining the abuse liability of this drug. The ability of drugs to reinforce operant responding in laboratory animals is a valid and reliable predictor of abuse potential. MDMA is self-administered by humans, but there have b...
Article
Exposure to a small amount of cocaine can trigger relapse, and so an understanding of the mechanisms underlying cocaine-seeking are important for the development of effective anti-relapse treatments. The present study sought to compare the contributions of dopamine D(1)- and D(2)-like receptors in drug-seeking produced by cocaine and WIN 35,428. Re...
Article
Repeated administration of cocaine produces sensitization to its locomotor-activating effects and increases the rate at which cocaine self-administration behavior is acquired. Methylphenidate is administered clinically on a daily basis, predominantly to children and adolescents, for the treatment of attention-deficit hyperactivity disorder (ADHD)....
Article
Systemic administration of caffeine reinstates extinguished cocaine self-administration behavior in rats, but the mechanism mediating this behavioral effect has not been established. The present study examined the role of adenosinergic A2 and dopaminergic mechanisms in caffeine-produced cocaine seeking. Following extinction of cocaine self-administ...
Article
It has been proposed that drugs that decrease cocaine self-administration or cocaine seeking by laboratory animals might be effective pharmacotherapies in the treatment of cocaine addiction. Previous studies have suggested that the dopamine uptake inhibitor, GBR 12909, might be such a candidate drug because it decreases cocaine self-administration....
Article
Previous research has indicated that pretreatment with the kappa-opioid receptor agonist, U69593, decreased the ability of experimenter-administered cocaine to reinstate extinguished cocaine self-administration behavior. This effect was specific to cocaine-produced drug seeking since U69593 failed to attenuate the ability of experimenter-administer...
Article
A number of studies have suggested that the continued presentation of stimuli associated with cocaine may contribute to drug-seeking and drug-taking. The influence of conditioned stimuli on the maintenance of self-administration has not, however, been systematically investigated. This study was designed to determine whether omission of a stimulus t...
Article
Previous studies showed that prior administration of kappa-opioid agonists decreased the development of sensitization to some of the behavioral effects of cocaine. The present study sought to determine whether the development of sensitization to cocaine's reinforcing effects was also sensitive to antagonism by kappa-opioid agonists. During a pretre...
Article
Manipulations of serotonergic systems have been shown to modify many of the behavioral effects of cocaine. It was recently demonstrated that serotonin (5-HT) depletions produced by inhibition of tryptophan hydroxylase reduced cocaine-seeking in an animal model. The present study was designed to determine whether pretreatment with specific 5-HT anta...
Article
A number of studies have demonstrated sensitization to the behavioral effects of cocaine following pretreatment. In most cases, pretreatments have been administered in the test environment. The present study determined the effects of home-cage administrations of cocaine on the acquisition of cocaine self-administration. Initial groups established t...
Article
Results of a previous study indicated that prior administration of the kappa-opioid receptor agonist, U69593, blocked the ability of cocaine to reinstate extinguished cocaine-taking behavior. In order to determine whether the effect of U69593 was specific to cocaine or was common to cocaine seeking produced by other dopamine uptake inhibitors, the...
Article
Rationale: Results of a previous study indicated that prior administration of the kappa-opioid receptor agonist, U69593, blocked the ability of cocaine to reinstate extinguished cocaine-taking behavior. Objectives: In order to determine whether the effect of U69593 was specific to cocaine or was common to cocaine seeking produced by other dopamine...
Article
Relapse to drug taking is a major obstacle to the effective treatment of cocaine abuse. Animal studies have determined that various drugs are able to reinstate extinguished drug-taking behavior. This study was designed to determine whether there is specificity in the ability of drugs to lead to cocaine-seeking and to compare potency and efficacy of...
Article
After repeated intermittent exposure to psychostimulants, an increase in the behavioral response to the drug is observed. The development of this sensitized response is greatly influenced by environmental cues. For example, when the pretreatments are administered in an environment distinct from the test, a sensitized response is often not observed....
Article
Previous research has shown that kappa-opioid receptor agonists decrease intravenous cocaine self-administration. These agents also block the development of sensitization that occurs following repeated exposure to cocaine, which is thought to be important in the maintenance and reinstatement of compulsive drug-seeking behavior. This study was desig...
Article
Previous data have shown that the repeated administration of kappa-opioid receptor agonists attenuates the acute behavioral effects of cocaine. The site and mechanism by which kappa-agonists interact with this psychostimulant, however, are unknown. Accordingly, the present microdialysis study characterized the effects of prior, repeated administrat...
Article
Full-text available
A great deal of research has focused on initiation into drug use and factors that increase the risk of initiation or protect against it. Initiation into the use of some drugs (such as alcohol) is extremely common, whereas initiation into use of other drugs (such as cocaine) is less frequent (Kandel 1975). Regardless of initiation rate, most individ...
Article
Repeated, intermittent administration of psychostimulants produces an enhancement of the subsequent behavioral effects of these drugs. This behavioral sensitization has been implicated in maintenance of and relapse to drug-taking. As a result, there has been great interest in elucidating the mechanisms underlying both the development and expression...
Article
Under some conditions, stimulant preexposure sensitizes rats to the reinforcing effects of cocaine and other stimulants, whereas under other conditions exposure decreases the reinforcing efficacy of cocaine. This paper reviews the literature on the effects of stimulant preexposure on self-administration, focusing on methodological and interpretativ...
Article
Previously, we demonstrated that caffeine dose-dependently reinstated extinguished cocaine-taking behavior in rats. In the present study, we determined whether this effect of caffeine would extinguish with repeated exposures. Rats were first trained to self-administered cocaine intravenously. Once reliable self-administration was obtained, the pump...
Article
Adult male rats ( Rattus norvegicus) were exposed to a water supply in the home cage containing 100 ppm cadmium chloride and sodium saccharin (.65% wt/vol; cadmium group) or water containing only the saccharin amendment (group control). On Day 65 of exposure, animals from each group received jugular catheter implants and were subsequently trained o...
Article
A substantial body of evidence has accumulated that implicates NMDA systems in the neural changes that are associated with the development of both electrical kindling of limbic sites and sensitization to the behavioral effects of repeated stimulant exposure. This study sought to establish whether electrical kindling of the brain was a sufficient co...
Article
A short self-report questionnaire that probed initial and most recent experiences with marijuana was administered to 197 undergraduate psychology students. Measures of Global Positive and Global Negative responses to marijuana use were obtained. There was substantial variability in the response to marijuana on both of these scales, which were moder...
Article
Ritanserin, a 5-HT2/1C antagonist, has been suggested to reduce the preference for cocaine in rats. In the present experiment, the action of ritanserin was investigated in locomotor activity, cocaine drug discrimination, and cocaine self-administration paradigms in rats. A low dose of ritanserin (1.0 mg/kg) was without effect on locomotor activity,...
Article
Interactions between caffeine and cocaine have been demonstrated in a number of behavioral paradigms. The present study was undertaken in an attempt to determine whether caffeine could reinstate extinguished cocaine-taking behavior in rats. Experienced self-administering rats were first put through extinction training. The rats were then given an i...
Article
Interactions between the effects of cocaine and caffeine have been demonstrated in tests of motor activity and drug discrimination. Since both drugs are widely consumed by humans, the present study was undertaken to determine whether a similar interaction between the reinforcing effects of these drugs could be demonstrated. Experienced cocaine self...
Article
This study assessed the enduring effects of amphetamine preexposure on the subsequent reinforcing effects of cocaine. Rats received nine daily injections of either d-amphetamine SO4 (2.0 mg/kg, IP) or vehicle 45 days prior to testing of the acquisition of cocaine (0.25 mg/kg/infusion) self-administration. The latency to acquire reliable cocaine sel...