Sex, Steroids, and Stimulant Sensitivity

Kuhn, Cynthia M.; Walker, Q. David; Kaplan, Karly A; Li, S. T.

doi:10.1111/j.1749-6632.2001.tb03565.x

Cited by 36 publications

(29 citation statements)

References 64 publications

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Section: Discussioncontrasting

confidence: 48%

“…The present study, however, noted effects on ICSS responding using systemic prazosin at doses of 0.5 and 2.0 mg/kg; doses that do not alter basal locomotion in an activity chamber [22,36] or in swim tests of spatial learning [37]. Moreover, in the present study, cocaine at 5.0 mg/kg markedly increased PR responding for ICSS, but in other studies this dose of cocaine is at the threshold for increasing locomotion in adult male rats [38,39].The present findings add to a growing body of literature in which antagonism of α1-ARs diminishes the behavioral effects of psychostimulants such as cocaine, morphine, amphetamine, and nicotine. Prazosin has been to shown to attenuate the hyperlocomotion induced by cocaine and amphetamine [19,21,22,40] and to block the locomotor sensitization induced by repeated cocaine or amphetamine administration [19,41].…”

contrasting

confidence: 48%

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Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

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The alkaloid lobeline inhibits the function of vesicular monoamine and dopamine transporters and diminishes the behavioral and neurochemical effects of nicotine and amphetamines. In the present study, we examined the interaction of systemic administration of lobeline on breakpoint scores on a progressive ratio (PR) schedule of intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB). Rats were run in two 30 min sessions, separated by a 10 min timeout period. At the end of the first session, each rat was injected with either 0, 0.5, 1.0 or 2.0 mg/kg (i.p.) lobeline. Positive controls known to suppress and to augment ICSS responding included the adrenergic antagonist prazosin (0, 0.5 and 2.0 mg/kg, i.p.) and the psychostimulant cocaine (0, 1.25, and 5.0 mg/kg, i.p.). Analyses of changes in average PR breakpoint scores between the 2 sessions revealed that lobeline significantly suppressed PR scores at doses of 0.5, 1.0 and 2.0 mg/kg, as did 0.5 mg/kg and 2.0 mg/ kg prazosin. These changes are unlikely to reflect motoric effects of these drugs inasmuch as neither lobeline nor prazosin alter locomotion at these doses. In contrast, PR breakpoint scores were significantly increased at 5.0 mg/kg cocaine, a dose that is sufficient to elevate locomotion in the rat. These results are consistent with the view that lobeline modulates brain reinforcement processes. Keywords Nicotinic receptors; Prazosin; CocaineMultiple behavioral assays can be used to index abuse potential [1][2][3] including the capacity of a drug to induce hyperlocomotion [4] and the capacity to induce conditioned place preference [5]. Rats will self-administer drugs such as cocaine or amphetamine into their vascular system [6]. Such drug infusions are thought to act on the neural substrates of reward. Electrodes placed along the path of the medial forebrain bundle (MFB) will support intracranial self-stimulation (ICSS) [7] and drugs of abuse are known to reduce the threshold current required to support ICSS [4,8,9]. Additionally, drugs of abuse are known to elevate progressive ratio (PR) responding for ICSS [10,11]. The latter types of studies are important in that a PR schedule, relative to a continuous reinforcement schedule, may be more sensitive to changes in reward engendered by neurotransmitter receptor antagonism [12].The alkaloid lobeline is derived from lobelia inflata [13]. Lobeline attenuates the hyperactivity induced by methamphetamine in rats and diminishes methamphetamine self-administration in rats [14][15][16]. The aforementioned results suggest that lobeline may function as a therapeutic tool for the treatment of methamphetamine abuse. Inasmuch as the impact of lobeline on ICSS responding has not been previously reported, the present study considered the impact of lobeline on breakpoints on a PR schedule of ICSS reinforcement. In this paradigm, the response requirement for reinforcement is increased systematically within a 30 min session [17]. Following completion of the first session, each rat was injected (i.p.)...

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Section: Discussioncontrasting

confidence: 48%

contrasting

confidence: 48%

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Wellman

Elliott

Barbee

et al. 2008

Physiology & Behavior

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“…Prior work confirms that males display place aversion or very modest preference for 10 mg/kg IP cocaine but strongly prefer higher IP doses (20 mg/kg; Nomikos and Spyraki 1988;Mayer and Parker 1993;Russo et al 2003b), whereas postpartum and virgin females prefer IP cocaine at lower doses (5-10 mg/kg; Russo et al 2003a, b;present study). This sharp gender contrast may be partially attributable to global endocrinological, physiological, and/or pharmacokinetic differences between males and females, previously proposed to underlie cycling females' heightened vulnerability to cocaine's motoric and motivational effects (Becker 1999;Kuhn et al 2001;Chin et al 2002;Hu and Becker 2003;Russo et al 2003a, b;Carroll et al 2004;. Notably, cocaine pharmacokinetics remain strikingly consistent across postpartum and cycling states following cocaine administration parameters similar to those used here (Vernotica and Morrell 1998;Wansaw et al 2005;see Dwivedi et al 1993 for recently parturient females).…”

Section: Discussionmentioning

confidence: 60%

Incentive salience of cocaine across the postpartum period of the female rat

et al. 2008

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Rationale-Objectives-Our prior conditioned place preference (CPP) work demonstrates that late (day16) postpartum female rats consistently prefer cocaine-over pup-associated chambers, whereas far fewer early postpartum (day8) females prefer the cocaine-associated chamber. The present study examines early and late postpartum females' preference for a cocaine-associated chamber when contrasted with a chamber associated with saline (rather than pups).Materials and methods-Postpartum females were tested for conditioned preference for chambers associated with cocaine (10 mg/kg subcutaneous (SC) or 0.5, 5, 10, or 20 mg/kg intraperitoneal (IP) injections) versus saline; preferences of virgin female and male rats for select cocaine stimuli (10mg/kg SC or IP) were also tested. Locomotion was recorded during CPP conditioning and testing.Results-Early and late postpartum females expressed strikingly similar preference for the cocaineassociated chamber across all administration routes and doses. IP cocaine produced an orderly, inverted U-shaped dose-preference curve, with preference peaking at the 5 mg/kg dose (83% of females). While many postpartum females preferred 10mg/kg cocaine administered either SC or IP, both virgin females and males expressed strong aversion to SC cocaine and, while virgin females strongly preferred IP cocaine, males remained relatively indifferent. Across 10mg/kg IP cocaineconditioning sessions, locomotor sensitization occurred exclusively in cocaine-but not salinepreferring postpartum females. Locomotor rate was lower in preferred versus nonpreferred chambers at CPP test.Conclusions-Early and late postpartum females may be equally and uniquely susceptible to sampling and/or abuse of modestly salient doses of cocaine (10mg/kg SC; 5mg/kg IP) compared to virgin females and/or males.

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“…Such a sex difference is well established in adult rats, and it has been attributed in large part to the potentiating effects of ovarian hormones in females (Becker, Molenda, & Hummer, 2001), whereas only minimal inhibitory effects of testosterone have been reported for males (Becker et al, 2001). Studies with cocaine have also found that sex differences emerge after puberty (Kuhn et al, 2001;Parylak et al, 2008), and prepubertal ovariectomy has been shown to decrease the behavioral effects of cocaine (Kuhn et al, 2001) and amphetamine (Forgie & Stewart, 1994) in adulthood. However, the effects of ovariectomy on drug responses in these studies were only examined in adulthood, so it is not clear whether lower circulating levels of ovarian hormones in adolescence contributed to age differences after amphetamine.…”

Section: Change In Activity To Second Administration Of Amphetaminementioning

confidence: 96%

“…This regulation likely develops in adolescence, as suggested by post-pubertal emergence of sex differences in sensitivity to cocaine (Kuhn, Walker, Kaplan, & Li, 2001;Parylak, Caster, Walker, & Kuhn, 2008) and by altered cocaine (Parylak et al, 2008) and amphetamine (Forgie & Stewart, 1994) sensitivity in adult female rats ovariectomized before puberty. Thus, to test whether differences in circulating ovarian hormones influence age differences in locomotor activity after amphetamine, we ovariectomized rats 6 days before amphetamine treatment either before puberty at P25, after puberty at P40, or in adulthood (P65).…”

mentioning

confidence: 96%

Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female rats

Mathews

Waters

McCormick

2009

Developmental Psychobiology

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We investigated hyposensitivity after amphetamine in early (postnatal Day 30; P30) and late (P45) adolescent rats compared to adults (P70) in experiment 1. Locomotor activity was measured for 1 hr after the first (acute) and second (24 hr later) injection of amphetamine (0.5 or 1.5 mg/kg). P30 and P45 rats were transiently hypoactive compared to adults, as indicated by reduced locomotor activity after acute amphetamine and enhanced activity after the second injection in adolescents only. In experiment 2, ovariectomy did not alter locomotor activity during habituation at any age compared to intact rats, and, as for intact adolescents, ovariectomized adolescents continued to be less active after amphetamine than adults, suggesting gonadal immaturity alone cannot account for age differences in experiment 1. However, ovariectomy attenuated the increase in activity after the second treatment. In experiment 3 involving untreated rats, tyrosine hydroxylase immunoreactivity was reduced in P30, P40, and P50 compared to P90 rats in the nucleus accumbens core and the medial prefrontal cortex. Thus, adolescents may have an increased threshold of behavioral activation that can be overcome with either a higher dose or with repeated amphetamine treatment, and may be related to changes in the dopamine system over development.

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Sex, Steroids, and Stimulant Sensitivity

Cited by 36 publications

References 64 publications

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

Incentive salience of cocaine across the postpartum period of the female rat

Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female rats

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