Sex Differences in Cocaine-Stimulated Motor Behavior Disparate Effects of Gonadectomy

Walker, Q. David; Cabassa, Jose; Kaplan, Karly A; Li, Shih-Tzung; Haroon, Jennifer; Spohr, Hilmar A; Kuhn, Cynthia M.

doi:10.1016/s0893-133x(00)00248-7

Cited by 112 publications

(99 citation statements)

References 51 publications

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“…The markedly greater locomotor response to MDMA observed in females is consistent with the enhanced response of female rats to many psychomotor stimulants including cocaine and amphetamine (Becker et al 1982;Festa and Quinones-Jenab 2004;Walker et al 2001). Two recent reports of increased locomotor responses to MDMA in females relative to males and in ovariectomized females following estrogen treatment are consistent with the present report (Pelenicek et al 2005;Zhou et al 2003).…”

Section: Discussionsupporting

confidence: 89%

“…In the present study, enhanced responses were observed even though females were used irrespective of estrous cycle stage: it is likely that responses of females during high-estrogen phases of the cycle are even higher than the mean response that we recorded. The largest stimulant responses in female rats are typically observed during high-estrogen phases of the cycle (Walker et al 2002), but significantly greater responses than males are observed even when females are used irrespective of cycle (Quinones-Jenab et al 1999;Sell et al 2000;Walker et al 2001). A recent report of enhanced locomotor responses in prepubertal male rats relative to females may well reflect that lack of ovarian steroid enhancement in prepubertal females (Koenig et al 2005).…”

Section: Discussionmentioning

confidence: 99%

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Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

et al. 2006

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Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). Objectives This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Methods Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Results Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temperature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. Conclusions MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

et al. 2006

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“…cocaine; Lynch and Roberts, 2004;Roberts et al, 2002). The idea that lower doses are required to produce sustained levels of intake in females compared to males is consistent with previous research showing that in females lower cocaine doses are necessary to induce stereotypy (Walker et al, 2001), and relapse responding .…”

Section: Discussionsupporting

confidence: 88%

Sex Differences in the Behavioral Effects of 24-h/day Access to Cocaine under a Discrete Trial Procedure

Lynch

Taylor

2003

Neuropsychopharmacol

118

116

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Although more men than women are addicted to cocaine, it has been suggested that women may have an accelerated transition to addiction, and that once addicted they may be more vulnerable to relapse. Here we investigate the effects of extended access to cocaine under a 24-h/day discrete trial procedure on patterns of intake and subsequent motivation to use cocaine as assessed by responding under a progressive-ratio schedule in male and female rats. Rats were initially trained to self-administer cocaine (1.5 mg/kg/infusion) under a fixed-ratio 1 schedule until acquisition occurred, and then responding was assessed under a progressive schedule for three sessions. Subsequently, rats had 24-h access to intravenous cocaine infusions (1.5 mg/kg) that were available in discrete trials (4, 10 min trials/h) for 7 consecutive days. At 10 days after the last discrete trial session, responding was reassessed under a progressive-ratio schedule for three additional sessions to investigate changes in motivation to obtain cocaine. Prior to cocaine self-administration under the 24-h access discrete trial procedure, males and females did not differ on cocaine self-administration under the fixed-ratio or progressive-ratio schedules. However, sex differences emerged under the 24-h access discrete trial procedure with females self-administering higher levels of cocaine, for longer initial periods of time, and showing a greater disruption in the diurnal control over intake than did males. Additionally, following a 10-day forced abstinence period, females responded at higher levels under the progressive-ratio schedule to obtain cocaine infusions than did males. These findings suggest that extended access to cocaine under the discrete trial cocaine selfadministration procedure produces sex-dependent patterns of intake and sex-specific changes in motivation to obtain cocaine as measured by progressive-ratio responding.

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“…Our laboratory and others have shown that indirect dopamine agonists like cocaine induce greater behavioral (Bowman and Kuhn, 1996;Walker et al, 2001a) and neuroendocrine (Walker et al, 2001b) effects in female than male rats. Female rats trained to self-administer cocaine on a progressive ratio schedule have higher break points than males (Roberts et al, 1987;Carroll et al, 2002), and acquisition, maintenance and reinstatement of cocaine self-administration are greater in female rats Carroll, 1999, 2000;Hu et al, 2004).…”

Section: Introductionmentioning

confidence: 78%

“…Haloperidol and quinpirole experiments used 120 pulse train duration at each frequency and post-drug recordings occurred at 5-10 min intervals beginning 10 min after drug administration. A shorter stimulus train duration (30 pulses) was used in the cocaine experiments to enable more frequent data collection so that all frequency responses could be recorded over the time of cocaine's peak behavioral effects (Walker et al, 2001a). Since sex differences in extracellular striatal dopamine concentrations develop with increasing stimulus train duration, the shorter stimulus duration also served to minimize baseline sex differences (Walker et al, 2000).…”

Section: In Vivo Proceduresmentioning

confidence: 99%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

121

106

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Previous data indicate that dopamine neurotransmission is differently regulated in male and female rats. The purpose of the present study was to investigate the dopamine transporter and autoreceptor as potential loci responsible for this sex difference. Fast cyclic voltammetry at carbon-fiber microelectrodes was used to monitor changes in electrically evoked levels of extracellular dopamine in the striata of anesthetized male and female rats before and after administration of an uptake inhibitor, a dopamine D 2 antagonist, or a D 3 /D 2 agonist. Administration of 40 mg/kg cocaine ip increased electrically-evoked extracellular dopamine concentrations in both sexes, but to a significantly greater extent in female striatum at the higher stimulation frequencies. The typical antipsychotic, haloperidol, increased dopamine efflux in both sexes but the effect was twice as large in the female striatum. The D 3 /D 2 agonist quinpirole induced an unexpected, transient increase in dopamine efflux following high-frequency stimulation only in females, and evoked dopamine was higher in females across this entire time course. More detailed analysis of cocaine effects revealed no fundamental sex differences in the interaction of cocaine with DAT in vivo or in synaptosomes. These results indicate that nigrostriatal dopamine neurotransmission in the female rat is more tightly regulated by autoreceptor and transporter mechanisms, perhaps related by greater autoreceptor control of DAT activity. Thus, baseline sex differences in striatal dopamine regulation induce different pharmacologic responses. These results contribute to understanding sex differences in stimulant-induced locomotor activity in rats and may have broader implications for neurologic disorders and their pharmacotherapies in humans.

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Sex Differences in Cocaine-Stimulated Motor Behavior Disparate Effects of Gonadectomy

Cited by 112 publications

References 51 publications

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

Sex Differences in the Behavioral Effects of 24-h/day Access to Cocaine under a Discrete Trial Procedure

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

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