Gender Effects Following Repeated Administration of Cocaine and Alcohol in Humans
Department of Psychiatry, Columbia University, New York, New York, United States Substance Use & Misuse
(Impact Factor: 1.23).
02/2005; 40(4):511-28. DOI: 10.1081/JA-200030693
Use of cocaine, alcohol, and the two drugs simultaneously is common and the risk of morbidity and mortality associated with these drugs is widely reported. This double-blind, placebo-controlled, randomized study examined gender differences in response to administration of these drugs alone and in combination.
Current users of cocaine and alcohol (n = 17) who met diagnostic criteria (DSM-IV) for cocaine dependence and alcohol abuse or dependence (not physiologically dependent on alcohol) and who were not seeking treatment for substance use disorders gave voluntary, written, informed consent to participate in three drug administration sessions:1) four doses of intranasal cocaine (1 mg/kg every 30 min) with oral alcohol (1 g/kg following the initial cocaine dose and a second drink at +60 min (120 mg/kg) calculated to maintain a plasma alcohol concentration of approximately 100 mg/dL; 2)four doses of cocaine and alcohol placebo; 3) cocaine placebo and alcohol. Pharmacokinetics were obtained by serial blood sampling, physiological measurements (heart rate and blood pressure) were obtained with automated equipment, and subjective effects were assessed using visual analog scales over 480 min.
Responses to cocaine, alcohol, and cocaine-alcohol were equivalent by gender for most measurements. Women had higher heart rates following alcohol administration (p = .02). Women consistently reported higher ratings for "Feel Good:' a measure of overall mental/physical well-being, for all study conditions, reaching statistical significance for cocaine (p = .05) and approaching significance for alcohol administration (p = .1).
Women showed equivalent responses to drug administration with the exception of perception of well-being, which was significantly increased for women. These findings may have implications for differential risk for acute and chronic toxicity in women.
Available from: Karran Phillips
- "We did not ask our participants to report the route of administration for each episode of use (though we did collect baseline data on each participant's preferred routes of administration). This limits our findings to some degree because sex differences in cocaine effects might themselves differ by route of administration (Collins et al., 2007; McCance-Katz et al., 2005; Mendelson et al., 1999; Sofuoglu et al., 1999 "
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Studies of sex differences have shown that men and women with drug-use disorders differ in course and outcome and in cue-induced activation of putative brain "control network" areas. We evaluated sex differences in daily functioning and subjective events related to drug use with ecological momentary assessment (EMA).
EMA data were collected from cocaine- and heroin-using outpatients (72 men; 42 women) in methadone maintenance in 2-5 randomly prompted (RP) entries per day and in participant-initiated entries for heroin or cocaine use or craving, for up to 25 weeks. Urine drug screens were conducted three times weekly. Data were analyzed via repeated-measures logistic regression, using sex as a predictor of responses.
In RP reports, women and men reported significantly different patterns of drug-cue exposure, with women significantly more likely to report having seen cocaine or been tempted to use in the past hour. Women also had higher craving after past-hour exposure to drug cues. In reports of drug use, women, compared to men, were more likely to report that they had used more cocaine than they had meant to, tended to feel guilty more often after drug use, and to have used despite trying not to use.
These findings provide real-time behavioral evidence that women respond differently than men to exposure to drug cues and to drug use, consistent with laboratory and brain-imaging findings. This information may be useful for development of sex-specific treatment strategies.
Available from: umich.edu
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ABSTRACT: The patterns of cocaine use differ between men and women. Women are more likely and take shorter time to become cocaine dependent after initial use of cocaine. Behavioral sensitization is an animal model that allows us to explore plastic changes with repeated cocaine use and to understand factors influencing this process, which may be involved in addition. This dissertation is trying to further characterize cocaine sensitization in females and to examine the role of ascending midbrain dopaminergic system in sex differences in cocaine sensitization. This dissertation first reports that cocaine sensitization promotes the acquisition of cocaine self-administration in females, suggesting the reinforcing effect is enhanced as a result of sensitization in females as in males. In addition, cocaine sensitization is suggested to be associated with enhanced midbrain dopamine neuron reactivity in males, which has not yet been tested in nucleus accumbens in vitro. This dissertation for the first time show that enhanced stimulated dopamine release in vitro from nucleus accumbens as well as striatum after cocaine experience in females, suggesting the same hypothesis is applicable in females as in males. Furthermore, estradiol treatment enhances behavioral sensitization in females when it is given with repeated cocaine treatment as predicted. More importantly, by comparing the cocaine-induced behavioral activation post sensitization on challenge day with or without additional estradiol treatment, acute estradiol treatment is first found to enhance cocaine-induced behavioral activation on cocaine-sensitized rats, suggesting estradiol produces an independent activating effect on sensitized neural circuits to affect behavioral sensitization. Lastly, cocaine sensitization and associated changes of dopamine neuron reactivity in the striatum are first compared between males and females in one experiment. Repeated cocaine treatment results in sexually dimorphic patterns of both cocaine sensitization and cross-sensitization to amphetamine. Accordingly, neuroadaptive changes of amphetamine-induced dopamine efflux in the striatum associated with sensitization also exhibit a sexually dimorphic pattern. It suggests sex differences in behavioral sensitization might be associated with sex differences in DA neuron reactivity in the striatum. This work improves our understanding of gender differences in patterns of cocaine abuse and has important implications for the development of gender-specific therapies in cocaine addiction. Ph.D. Psychology University of Michigan, Horace H. Rackham School of Graduate Studies http://deepblue.lib.umich.edu/bitstream/2027.42/61686/1/zhaowei_1.pdf
Available from: Andrey Verendeev
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ABSTRACT: We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.
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