Robert Carey

State University of New York Upstate Medical University | SUNY Upstate Medical · Department of Psychiatry and Behavioral Sciences

This investigation was undertaken to compare the sensitization/conditioned effects induced by apomorphine given pre-trial versus administered immediately post-trial or 15 min post-trial. We measured the effects on locomotor activity of 5 daily apomorphine treatments induced by an inhibitory low auto-receptor dose (0.05 mg/kg) and a stimulatory high...

Morphine has potent pro-dopamine effects that can be manifested as hyper-locomotion and these behavioral effects can undergo conditioning and sensitization. The aim of the present study was to assess whether an inhibitory dopaminergic post-trial treatment (0.05 mg/kg apomorphine) given during re-consolidation could reduce morphine conditioning. To...

The activation of extracellular signal-regulated kinase protein (ERK) has been linked to the adaptive responses to environmental changes and memory. The aim of this study was to measure ERK activation in primary dopamine projection areas namely, the prefrontal cortex and the nucleus accumbens following a conditioned dopaminergic drug response. Init...

In contextual drug conditioning, the onset of the drug treatment is contiguous with the contextual cues. Evidence suggests that drug conditioning also can occur if there is a discontinuity between the onset of the drug effect and offset of the contextual cues. Here we examine whether post-trial contextual drug conditioning conforms to several Pavlo...

Rationale Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. Objective Assess the role of the amygdala in emotional responses. Methods Experimental manipulations were performed in which environmental familiarity was the variable. To provide...

Presentation of non-aversive light stimuli for several seconds was found to reliably induce locomotor activation and exploratory-like activity. Light-induced locomotor activity (LIA) can be considered a convenient simple model to study sensory-motor activation. LIA was previously shown to coincide with serotonergic and dopaminergic activation in sp...

The Pavlovian conditioning of drug effects has frequently been demonstrated using protocols that are variants of Pavlovian delay conditioning. We undertook to determine if drug conditioning could be induced using a Pavlovian trace conditioning procedure. Rats were tested in a novel open-field environment for 5minutes and in post-trial phase were in...

Serotonin containing neurons are located in nuclei deep in the brainstem and send axons throughout the central nervous system from the spinal cord to the cerebral cortex. The vast scope of these connections and interactions enable serotonin and serotonin analogs to have profound effects upon sensory/motor processes. In that conditioning represents...

Pavlovian conditioning of drug effects is generally acknowledged to be a critical factor in the development and persistence of drug addiction. In drug conditioning the focus has essentially been on one type of Pavlovian conditioning, namely, delay conditioning in which the CS and drug UCS overlap and are temporally contiguous. Another type of Pavlo...

Psychostimulant conditioning and sensitization effects have proven to be difficult to eliminate using behavioral methods. We used a low autoreceptor dose of apomorphine in counter-conditioning and memory re-consolidation protocols to modify conditioned and sensitized responses induced by a high dose of apomorphine. Rats received five daily treatmen...

Bilateral lesions in the septal area of rats were found to independently increase water intake and operant responding for water on a DRL reinforcement schedule. These findings indicate that separate mechanisms for regulating appetitive consumatory behavior and response inhibition are present in the septal area.

Bilateral septal ablations in rats increased resistance to extinction when made before training, but decreased resistance when made after training. These contrasting effects were considered to demonstrate that septal ablations affect retention as well as performance.

Both typical and atypical antipsychotic drugs are D2 receptor antagonists but yet appear to have markedly different effects upon the induction of dopamine sensitization. This study aims to compare the effects of subchronic regimens of low-dose olanzapine and haloperidol administered to rats previously sensitized to apomorphine. Initially, rats rece...

The effect of a 1-mg/kg dose of d-amphetamine on the acquisition of a temporal discrimination occasioned by the reinforcement contingencies of a DRL 22-sec schedule was investigated. After 19 DRL sessions under amphetamine, a temporal discrimination appropriate to the DRL contingencies was developed. On the 20th DRL session, saline rather than amph...

Rationale: Anti-psychotic drugs are antagonists of dopamine D2 receptors and repeated administration may lead to the development of dopamine receptor supersensitivity. Objectives: The objective of this study is to investigate the effects of sub-chronic olanzapine treatments upon the induction of dopamine receptor supersensitivity. Methods: Rat...

Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.05mg/kg) and a high (2.0mg/kg) dose were used to inhibit or to enhance dopamine act...

Anti-psychotic drugs are antagonists at the dopamine D2 receptors and repeated administration can lead to the development of dopamine receptor supersensitivity. In two experiments, separate groups of rats were administered 10 daily low or high doses of the typical anti-psychotic drug haloperidol (0.03 or 1.0 mg/kg). The high dose decreased locomoti...

Psychostimulant sensitization can have transformative effects upon contextual stimuli such as acquired conditioned stimuli and conditioned incentive motivational properties. The aim of this study is to induce apomorphine sensitization and conduct non-drug exposures to the contextual cues followed by post-trial treatments designed to associate incre...

Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of apomorphine (2.0 mg/kg). Two days f...

Cocaine is a major stimulant drug which can have rewarding and locomotor activating effects. It is used by non-addicts to enhance concentration and performance in a work or social setting. It was suggested that cocaine may amplify the impact of mood and sensory stimulation on behaviour. Here we tested whether cocaine can enhance the impact of novel...

We investigated environmental contrast effects on the expression of apomorphine locomotor sensitization by using two arena formats (round and square) that elicited differential levels of spontaneous locomotion. Eight groups of rats received 3 daily injections of apomorphine (APO) (2.0mg/kg) or vehicle (VEH) to induce locomotor sensitization: four g...

Clinical interventions which produce cue and contextual extinction learning can reduce craving and relapse in substance abuse and inhibit conditioned fear responses in anxiety disorders. In both types of disorders, classical conditioning links unconditioned drug or fear responses to associated contextual cues and result in enduring pathological res...

This chapter provides a brief synopsis of the essential role of brain serotonergic neurons in the integration of sensory input and motoric output. Although serotonin neurons are proportionally small numerically in the brain, the serotonin neurons have anatomical communication with virtually all neurons in the brain. For sensory-motoric function, th...

Repeated treatments with psychostimulant drugs generate behavioral sensitization. In the present study we employed a paired/unpaired protocol to assess the effects of repeated apomorphine (2.0 mg/kg) treatments upon locomotion behavior. In the first experiment we assessed the effects of conditioning upon apomorphine sensitization. Neither the extin...

In the study of behavioural sensitization induced by dopamine agonists, D1 and D2 receptors have a critical, but a puzzling role. The objective of this study is to examine the effects of the D1 antagonist SCH-23390 and the D2 antagonist sulpiride given repeatedly alone or in combination with apomorphine upon apomorphine conditioning and sensitizati...

Low dose apomorphine treatments preferentially activate dopamine autoreceptors and inhibit dopamine neurons as well as behavior. In contrast, high doses of apomorphine induce locomotor stimulation by activating dopamine postsynaptic receptors. We compared the effects of low (0.05 mg/kg) vs. high (2.0 mg/kg) repeated apomorphine treatments (5) using...

Conditioned opiate reward (COR) is rapidly acquired and slowly extinguished. The slow rate of extinction of the salience of drug-related cues contributes to drug craving and relapse. The gamma-aminobutyric acid receptor type B (GABA(B)) agonist, baclofen, attenuates the unconditioned rewarding actions of several drugs of abuse and was investigated...

High doses of apomorphine induce sensitization to locomotor stimulant effects whereas low doses induce locomotor inhibition. We examined whether repeated low dose apomorphine induced sensitization and conditioning to the locomotor inhibitory effect. Three doses of the D1/D2 agonist, apomorphine, were used in a Pavlovian conditioning protocol: 0.05...

In order to investigate the contribution of serotonergic effects of cocaine to Pavlovian conditioning of cocaine locomotor stimulant effects, two experiments were conducted in which groups of rats (N = 10) received cocaine treatments (10 mg/kg) paired or unpaired to placement in an open-field environment. Initially, a cocaine conditioned locomotion...

Application of cocaine or exposure to cocaine-related stimuli induces widespread activation of the cortex in neuroimaging studies with human subjects. In accordance to these findings, it was reported in previous microdialysis experiments that cocaine increased serotonin (5-HT) and dopamine in various cortical brain areas. The present series of stud...

This study examined the onset of locomotor sensitization induced by apomorphine as a function of the temporal delay between drug injection and testing. In experiment 1, rats received three daily administrations of 2.0 mg/kg apomorphine or vehicle either immediately (0 min) or 20 min before being placed into the test environment for 20 min test sess...

The serotonergic system has a broad influence on behavior, but its specific contribution to novel object exploration remains to be examined. Toward this end, we assessed the impact of the 5-HT1A agonist, 8-OHDPAT (0.01-0.05 mg/kg) and the 5-HT1A antagonist, WAY-100635 (0.01-0.05 mg/kg) on novel object exploration in a familiar open-field environmen...

Whether cocaine locomotor conditioning represents a cocaine positive effect; i.e., a Pavlovian cocaine conditioned response; or, a cocaine negative effect; i.e., interference with habituation to the test environment, is a subject of some controversy. Three separate experiments were conducted to compare the behavior (locomotion and grooming) of sepa...

The emotional effects of the initial consumption of cocaine can have a strong influence on the subsequent use of this drug. Several studies in rodents using long test latencies have reported anxiogenic effects of cocaine. Anxiogenesis, however, would seem to contradict cocaine's well known rewarding effects and its abuse liability. The present stud...

Cocaine-induced increases in dopamine (DA) contribute importantly to cocaine effects on behavior but, the role of concomitant increases in norepinephrine (NE) and serotonin (5-HT) is less well understood. In order to selectively block the increases in NE and 5-HT evoked by cocaine, autoreceptor preferring low doses (0.01, 0.025 and 0.05 mg/kg) of t...

The dopaminergic (DA) and serotonergic (5-HT) systems are modulatory transmitter systems that can influence a wide range of behavioural functions. Psychostimulant drugs increase both DA and 5-HT activity by substance-specific mechanisms and, consequently, can broadly influence behavioural and emotional processes in humans and animals. In this chapt...

It is well established that cocaine stimulant effects are potentiated in a novel environment. The relationship between cocaine and novel stimuli, however, remains poorly understood. In this study, we examined the effects of different dose levels of cocaine (5.0, 10.0 and 20.0 mg/kg) administered to separate groups of rats (N=10) on attentional beha...

Neuroimaging studies with humans showed widespread activation of the cortex in response to psychostimulant drugs. However, the neurochemical nature of these brain activities is not characterized. The aim of the present study was to investigate the effects of cocaine and d-amphetamine on dopamine (DA) and serotonin (5-HT) in cortical areas of the hi...

7-OH-DPAT is a dopamine D2/D3 agonist, which at low doses acts preferentially on D3 receptors but at high doses it acts on D2 and D3 receptors. The present study investigated the contribution of D3 and D2 receptors on latent inhibition (LI) by using two dose levels of 7-OH-DPAT: a low dose, 0.1 mg/kg (D3 receptor activation) and a high dose, 1.0 mg...

The present study examined the minimal number of exposures to the D1/D2 agonist apomorphine capable of producing behavioral sensitization. Rats received one (experiment 1) or two administrations on two successive days (experiment 2) of apomorphine (0.5 and 2.0 mg/kg) paired or unpaired to an open-field environment. After 2 days of drug withdrawal,...

Serotonin(1A)-receptors (5-HT(1A)-Rs) are important components of the 5-HT system in the brain. As somatodendritic autoreceptors they control the activity of 5-HT neurons, and, as postsynaptic receptors, the activity in terminal areas. Cocaine (COC), amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine ("Ecstasy", MDMA)...

The 5-hydroxytryptamine (5-HT)(2C) receptor has received considerable attention as a target for treating drug addiction. 5-HT(2C)-receptor agonism, however, also induces side-effects. In this article, we review recent findings regarding the involvement of 5-HT(2C) receptors in behaviours related to drug addiction in animals. It was recently shown t...

The behavioral and neurobiological impact of cocaine can be strongly influenced by the environmental context in which the cocaine effects are experienced. In this report, we present the results of an experimental study in which the effects of environmental context in terms of novelty/familiarity upon locomotor stimulant effects of cocaine were exam...

The present study examined the role of D(1) and D(2) receptors in the conditioning of apomorphine-induced locomotor behavior. A Pavlovian conditioning protocol was used in which rats received 5 daily intrastriatal apomorphine treatments paired or unpaired to an open-field environment followed, 2 days later, by a saline test for conditioning. In the...

Repeated cocaine treatments typically generate sensitization effects which are environment specific. In this study, we investigated whether drug treatments with highly selective receptor specificity can also function as contextual cues to control the expression of cocaine sensitization effects. Two experiments were conducted in which separate group...

Recently it was shown that the combined pretreatment with low autoreceptor preferring dose levels of apomorphine (0.05 mg/kg) and 8-OHDPAT (0.05 mg/kg), which decrease dopaminergic and serotonergic activity, induces a profound behavioral inhibition and also blocks the stimulant effects of cocaine. In two experiments, we report that the acute blocka...

Diethylpropion (1-phenyl-2-diethylamine-1-propanone hydrochloride) is a stimulant drug with reinforcing properties that is used to treat obesity in humans. While the anorectic properties of diethylpropion are mediated by a noradrenergic mechanism, stimulant properties depend on its effects on the serotonergic (5-HT) and/or dopaminergic systems. In...

Cocaine is a potent stimulant drug, but its stimulant effects can be substantially modulated by environmental novelty versus familiarity. In this report, we varied exposures to a novel environment as a way to assess the impact of environmental familiarity versus novelty upon the locomotor activation induced by acute and chronic cocaine treatments....

The psychostimulant effects of cocaine critically depend on the serotonergic (5-HT) system, of which the 5-HT1A receptor is an essential component. We recently showed divergent contributions of various pre- and postsynaptic 5-HT1A receptor populations to the behavioral effects of cocaine. Here, we further investigate the role of 5-HT1A autoreceptor...

The pairing of cocaine treatments with a specific test environment typically leads to cocaine-conditioned drug effects. In this study, we first pre-exposed rats 10 times to an open-field environment to establish an habituation asymptote in locomotor activity prior to the initiation of cocaine treatments. Two groups (N=10) equated for locomotion, gr...

Diethylpropion (1-phenyl-2-diethylamine-1-propanone hydrochloride) is a stimulant drug with reinforcing properties that is used to treat obesity in humans. While the anorectic properties of diethylpropion are mediated by a noradrenergic mechanism, stimulant properties depend on its effects on the serotonergic (5-HT) and/or dopaminergic systems. In...

The contribution of the 5-HT(1A) somato-dendritic autoreceptor populations to spontaneous and cocaine-induced locomotion is unclear. To use a low dose range of +/-8-hydroxy-2-(di- n-propylamino)tetralin (8-OHDPAT) to preferentially stimulate 5-HT(1A) autoreceptors and a medium 8-OHDPAT dose range to stimulate both 5-HT(1A) autoreceptors and postsyn...

'Active immobility' (AI) is an independent behaviour that can be characterized by behavioural immobility, an increased muscular rigidity and the sustaining of an unusual posture. In previous studies with cocaine we observed, concomitant with hyperlocomotion and increased rearing activity, an increase in AI in well-habituated animals, which may cons...

We used the D(2) receptor agonist, apomorphine (APO) and the 5-HT(1A) receptor agonist, 8-OHDPAT (8OH) in a low dose range to stimulate autoreceptors and in this way assess the separate and combined effects of reduced DA and 5-HT activity upon spontaneous and cocaine induced locomotor behavior. Two separate experiments were conducted. In the first...

The nucleus accumbens (Nac) is an important structure for cocaine-induced hyperactivity and receives a dense serotonergic (5-HT) innervation. Previous studies showed that a systemic activation of 5-HT(1A) receptors potentiates cocaine-induced hyperlocomotion, but attenuates the cocaine-induced 5-HT increase in the Nac. In order to address the role...

Cocaine induces an increase in hippocampal and nucleus accumbens (Nac) serotonin (5-HT) concentration parallel to locomotor activation. Both effects can be modulated by systemic 5-HT(1A)-receptor agonism/antagonism. Given the contribution of the hippocampus to spontaneous behavioral activity, these observations suggest a role for hippocampal 5-HT a...

Non-human primates provide important insights into the potential use of 5-HT(1A) receptor antagonists in treating human anxiety disorders and as research tools, given the existent inconsistencies in rodent tests. This study investigated the effects of the selective silent 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N...

In C57BL/6 mice, pretreatment with GABA(B) receptor agonist baclofen blocked the rewarding effects of morphine as measured by acquisition of conditioned place preference. Fos immunoreactivity, a neuronal activity marker, was induced in opiate conditioned mice in several forebrain regions including the nucleus accumbens core and shell, anterior cing...

Although the dopaminergic system still plays an important role in the investigation of the behavioral effects of cocaine, a broad literature emerged parallel to this research that provided significant evidence for an important contribution of the serotonergic (5-hydroxytryptamine, 5-HT) system. It has been known for a long time that the 5-HT transp...

An animal's response to novelty has been suggested to be a predictor of its response to drugs of abuse. The possible relationship between an individual's behavioral response to novelty and its subsequent behavioral response to cocaine has not been subjected to a detailed correlational analysis. To use a repeated cocaine treatment protocol to induce...

Although the dopaminergic system still plays an important role in the investigation of the behavioral effects of cocaine, a broad literature emerged parallel to this research that provided significant evidence for an important contribution of the serotonergic (5-hydroxytryptamine, 5-HT) system. It has been known for a long time that the 5-HT transp...

The hippocampus and the nucleus accumbens (Nac) are important structures for the modulation of spontaneous locomotor activity. Both structures receive a serotonergic (5-HT) innervation. We have previously reported that the 5-HT(1A)-receptor antagonist WAY 100635 blocked cocaine-induced hyperactivity, while potentiating cocaine-induced 5-HT increase...

Cocaine has potent locomotor stimulant effects in rodents, which seemingly can become conditioned to test environment cues. In two experimental protocols, we measured the effects of cocaine on locomotor activity and grooming behavior, and subsequently tested whether these cocaine effects became conditioned to contextual cues. In the first experimen...

An increase in the extracellular dopamine (DA) concentration is generally accepted as an important neurochemical mediator of the behavioral effects of cocaine. Cocaine induced increases in serotonergic (5-HT) activity also appears to be involved in these effects. Here we describe the effects of the 5-HT(1A)-receptor antagonist WAY 100635 on the beh...

The hippocampus is an important mediator of learning and reinforcement, but its role in cocaine effects has received little attention. Neuronal activity in the hippocampus and the nucleus accumbens (Nac) depend on serotonergic (5-HT) transmission. Here we describe for the first time a cocaine-induced increase in 5-HT concentration in the hippocampu...

The effects of the 5-HT1A agonist, (+/-)-8-hydroxy-dipropylaminotetralin (8-OHDPAT) upon the unconditioned and conditioned behavior induced by cocaine were assessed in rats. Separate groups (n=7) received saline, cocaine (10 mg/kg), 8-OHDPAT (0.2 mg/kg), or 8-OHDPAT (0.2 mg/kg) plus cocaine (10 mg/kg) for eight treatment sessions (two per week) in...

The 5-HT1A receptor site has been demonstrated to be an important pharmacological target in the modulation of unconditioned behavioral effects induced by cocaine. In this study, separate groups of rats (n=7) received a series of the 5-HT1A agonist treatments, 8-OHDPAT (0.2,0.4 mg/kg) in combination with saline or cocaine (10 mg/kg). Using a crossov...

Cocaine induced locomotor stimulant effects are generally attributed to cocaine effects on brain dopamine. In this report, we present evidence that the 5-hydroxytryptamine1A (5-HT1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) and the 5-HT1A antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cycylhexanecarboxami...

In the first experiment, separate groups of rats (n = 7) were treated with either saline, cocaine (10 mg/kg), haloperidol (0.1 mg/kg), or cocaine (10 mg/kg) plus haloperidol (0.1 mg/kg). Locomotor behavior was measured in an open-field environment, and cocaine induced a reliable locomotor stimulant effect compared to saline-treated animals. Haloper...

Cocaine treatments of 2.5, 5.0, 10.0 and 15.0 mg/kg induced dose-dependent increases in locomotor behavior. This cocaine-induced increase in locomotion was blocked if the animals were administered the selective 5-HT(1A) antagonist, WAY 100635 (0.4 mg/kg) prior to the cocaine treatment. The 0.4-mg/kg dose of WAY 100635 did not affect locomotor behav...

Cocaine conditioned stimuli are capable of eliciting cocaine craving in individuals with a history of cocaine use. As a consequence, there have been a number of attempts using animal models to identify pharmacological treatments which can attenuate cocaine conditioned effects. The emphasis in these studies has been to employ drug doses which do not...

The development of sensitization to the behavioral effects of cocaine occurs with repeated intermittent usage. In the present study rats were given five daily IP injections of cocaine (10 mg/kg) immediately prior to placement in an open-field environment for 20 min to induce cocaine sensitization. Control groups received saline injections or cocain...

The effects of MK-801 upon motor activity and memory were assessed in a novel use of open-field behavior testing. In this study, rats were treated with different doses of MK-801 (0.025, 0.05, 0.1 and 0.2 mg/kg) and given a brief 10-min exposure to an open-field in which locomotor activity and within-session habituation were measured. Doses of MK-80...

With repeated cocaine use, cocaine conditioned behavior develops to associated stimuli, and in addition, sensitization can occur to the unconditioned stimulant effects of cocaine. To investigate the relationship between the conditioned and unconditioned behavioral effects of repeated cocaine use, two groups of rats (n = 7) were given five daily pai...

The identification of the Pavlovian conditioning of the behavioral effects of cocaine using open-field behavior is often confounded by the concurrent occurrence of behavioral habituation in control animals. Thus, differences in spontaneous activity between cocaine conditioned animals vs. control can be explained either by Pavlovian conditioning of...

This report details a new method to measure habituation in an open-field. In addition to the measurement of spontaneous locomotor activity, time spent per visit to the center zone (CZ) is also measured. Critically, a small object is placed in the CZ to modulate an animal's investigatory response. When an animal is first exposed to the open-field, t...

L-DOPA can often induce psychotic reactions during treatment for Parkinson's disease. This study was undertaken to assess, in an animal model of Parkinson's disease, the impact of L-DOPA treatment on two potential biological risk factors for psychosis, namely, an increase in prefrontal cortex dopamine and an increase in the stress-related hormone c...

Antagonism of the NMDA receptor with MK-801 is considered to be an effective pharmacologic manipulation to prevent the development of sensitization effects to drugs such as cocaine. The present study investigated this issue by comparing the behavioral response of separate groups of rats to three treatment cycles of either saline, 0.1 mg/kg MK-801,...

The role of the N-methyl-D-aspartate (NMDA) receptors in cocaine conditioning and sensitization of locomotor activity was studied in four groups of Sprague-Dawley rats. A sub-motoric dose of the NMDA antagonist MK-801 (0.1 mg/kg, i.p.) was employed using a novel dual-compartment Pavlovian drug conditioning paradigm. The animals were placed sequenti...

We describe a simplified HPLC method for the measurement of cocaine and catecholamines in the same brain tissue sample. Using this method to measure cocaine in the brain of rats which received either 10 or 20 mg/kg cocaine injections, we found substantial cocaine concentration differences between medial prefrontal cortex, striatum and limbic brain...

We had previously found that in animals with moderate nigro-striatal dopamine (DA) lesions (i.e. 45-65% residual neostriatal DA) the mixed D1/D2-agonist apomorphine induced ipsiversive rather than the usual contraversive turning found after more radical DA lesions. Since this result promised to provide a behavioral animal model for pre-clinical Par...

This study, which used an animal model of Parkinsonism, evaluated whether the NMDA antagonist MK-801 can prevent the development of L-3-4-dihydroxyphenylalanine (L-DOPA) sensitization. In separate groups, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were treated with saline, 25 mg/kg L-DOPA methyl ester, 0.1 mg/kg MK-801, or MK-801 plus...