Discriminative stimulus properties of pentobarbital and progesterone in male and female rats

Heinsbroek, Rob P.W.; Haaren, Frans van; Zantvoord, Frans; Poll, Nanne E. van de

doi:10.1016/0091-3057(87)90455-2

Cited by 22 publications

(5 citation statements)

References 11 publications

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“…The finding of drug-appropriate responding engendered by both neuroactive steroids is consistent with previous data in pentobarbital-trained rats, in which the endogenous neuroactive steroids THDOC and allopregnanolone produced dose-dependent increases in drug-appropriate responding (Ator et al 1993). Progesterone, the steroid precursor to pregnane neuroactive steroids, also exhibited discriminative stimulus effects similar to pentobarbital in rats (Heinsbroek et al 1987). In addition to results with pentobarbital as the training drug, certain neuroactive steroids have also been shown to engender full drugappropriate responding in subjects trained to discriminate other GRC positive modulators.…”

Section: Discussionsupporting

confidence: 90%

Reinforcing and discriminative stimulus effects of the neuroactive steroids pregnanolone and Co 8-7071 in rhesus monkeys

Rowlett

Winger

Carter³

et al. 1999

Psychopharmacology

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Section: Discussionsupporting

confidence: 90%

Reinforcing and discriminative stimulus effects of the neuroactive steroids pregnanolone and Co 8-7071 in rhesus monkeys

Rowlett

Winger

Carter³

et al. 1999

Psychopharmacology

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“…Progesterone often shares discriminative stimulus effects with drugs that act as general depressants. For example, progesterone produced pentobarbital-like discriminative stimulus effects in ovariectomized, but not in gonadally intact female or male rats (Heinsbroek et al, 1987). In monkeys, allopregnanolone, a major metabolite of progesterone, produced ethanol-like discriminative stimulus effects and the degree of substitution varied across menstrual cycle phase (Grant et al, 1997).…”

Section: Interactions Between Cocaine and Neuroactive Steroid Hormonesmentioning

confidence: 98%

Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

Mello

Knudson

Kelly

et al. 2011

Neuropsychopharmacol

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The neuroactive steroid hormone progesterone attenuates cocaine's abuse-related effects in women and in rodents under some conditions, but the effects of testosterone are unknown. We compared the acute effects of progesterone (0.1, 0.2, and 0.3 mg/kg, intramuscularly (i.m.)), testosterone (0.001, 0.003, and 0.01 mg/kg, i.m.), and placebo on cocaine self-administration and cocaine discrimination dose-effect curves in female rhesus monkeys. Cocaine self-administration (0.03 mg/kg per inj.) was maintained on a fixed ratio 30 schedule of reinforcement, and monkeys had unlimited access to cocaine for 2 h each day. Cocaine doses were administered in an irregular order during each dose-effect curve determination, and the same dose order was used in each subject in all treatment conditions. Blood samples for hormone analysis were collected at the end of each test session. Banana-flavored food pellets (1 g) were also available in three 1-h daily sessions. In drug discrimination studies, the effects of pretreatment with progesterone (0.032-0.32 mg/kg, i.m.) and testosterone (0.001-0.01 mg/kg, i.m.) on the discriminative stimulus effects of cocaine (0.18 mg/kg, i.m.) were examined. Progesterone and testosterone did not alter cocaine discrimination, and did not substitute for cocaine. In contrast, progesterone and testosterone each significantly decreased cocaine self-administration, and produced a downward and rightward shift in the cocaine self-administration dose-effect curve. These findings are concordant with clinical reports that progesterone administration may decrease ratings of positive subjective effects of cocaine in women, and suggest the possible value of neuroactive steroid hormones for the treatment of cocaine abuse and reduction of risk for relapse.

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“…Within the GABAergic system, drug discrimination procedures have been used to determine similarities among the GABA A receptor ligands (Ator 1990). For example, progesterone and its metabolite allopregnanolone have discriminative stimulus effects similar to pentobarbital (Heinsbroek et al 1987;Ator et al 1993). For example, progesterone and its metabolite allopregnanolone have discriminative stimulus effects similar to pentobarbital (Heinsbroek et al 1987;Ator et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Ethanol-like discriminative stimulus effects of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in femaleMacaca fascicularis monkeys

et al. 1996

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The present study was designed to characterize the discriminative stimulus effects of ethanol and the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) in non-human primates. Female cynomolgus monkeys (Macaca fascicularis) were trained in a two-lever procedure to discriminate 1.0 g/kg ethanol (IG, 30 min pretreatment) from water using food reinforcement. Consistent with previous results in a variety of species, pentobarbital (0.56-17 mg/kg, IG) resulted in a dose-dependent substitution for the discriminative stimulus effects of ethanol, with an average ED50 value of 1.9 mg/kg. Administration of allopregnanolone (0.3-5.6 mg/kg, IV) also produced complete substitution for the discriminative stimulus effects of ethanol, with an ED50 value of 1.0 mg/kg. Plasma allopregnanolone levels 35 min following the administration of 3.0 mg/kg allopregnanolone ranged from 33 to 69 ng/ml. The ethanol-like discriminative stimulus effects of 1.0 mg/kg allopregnanolone (IV) were present for 60 min, with a return to complete water-appropriate responding at 90 min post-treatment. The results indicate that the endogenous neuroactive steroid allopregnanolone produces subjective effects in cynomolgus monkeys that are similar to ethanol. These findings suggest that changes in the endogenous levels of allopregnanolone could alter sensitivity to the subjective effects of ethanol.

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Discriminative stimulus properties of pentobarbital and progesterone in male and female rats

Cited by 22 publications

References 11 publications

Reinforcing and discriminative stimulus effects of the neuroactive steroids pregnanolone and Co 8-7071 in rhesus monkeys

Reinforcing and discriminative stimulus effects of the neuroactive steroids pregnanolone and Co 8-7071 in rhesus monkeys

Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

Ethanol-like discriminative stimulus effects of the neurosteroid 3α-hydroxy-5α-pregnan-20-one in femaleMacaca fascicularis monkeys

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