Sex differences in physical dependence on orally self-administered phencyclidine (PCP) in rhesus monkeys (Macaca mulatta).

Abstract

Withdrawal from orally self-administered phencyclidine (PCP) has been shown to alter operant baselines of food-maintained responding. The goal of the present study was to determine whether there are sex differences in these alterations. Seven female and 7 male rhesus monkeys (Macaca mulatta) were given concurrent access to PCP and water under fixed ratio (FR) 8 schedules during 2 daily sessions that alternated with 2 sessions during which pellet deliveries were contingent on lever presses under an FR 64 schedule. After operant responding stabilized, PCP was replaced by water for 10 days, and food access remained under the same schedule. Subsequently, concurrent PCP and water access was reintroduced for 10 days. This procedure was repeated with 3 PCP concentrations (0.125, 0.25, and 0.50 mg/ml) and 3 FR requirements for food-reinforced responding (64, 128, and 256). Disruptions in operant responding for food served as a quantitative measure of withdrawal severity. During PCP withdrawal, males showed a greater suppression of food-maintained behavior than females at the 2 highest PCP concentrations and the lowest FR requirement tested. Males responded more than females for PCP; however, when weight was taken into consideration, PCP intake (milligrams per kilogram) in males and females was equal. The data suggest that males may experience more severe withdrawal effects than females, and the duration of the adverse effects of withdrawal lasts longer in males than in females. This study is the 1st to use nonhuman primates to document sex differences in withdrawal severity as measured by a quantifiable baseline.

Impulsivity as a behavioral measure of withdrawal of orally delivered PCP and nondrug rewards in male and female monkeys

“…These results were consistent with those of Perry et al (2006) who found that PCP withdrawal disrupted foodmaintained performance (FR 64) to a greater extent in males than females. In the present study, the MAD values for SACC during PCP FR access were not different than during BL-W; thus, PCP intake did not alter impulsivity for SACC, while PCP withdrawal clearly increased it.…”

“…Recent work measuring changes in food-maintained responding during PCP withdrawal indicated that male monkeys showed a more severe and longer duration of behavioral withdrawal effects than females when PCP access was terminated (Perry et al 2006). These results were consistent with studies in rats injected with pentobarbital, ETOH (Devaud and Chadda 2001), morphine (Cicero et al 2002;e.g., Suzuki et al 1985), and methaqualone (Suzuki et al 1988).…”

“…Physical dependence on self-administered drugs has been modeled in preclinical research by establishing selfadministration and then removing drug access and measuring disruptions in operant responding reinforced by food or other nondrug rewards in rats (e.g., Barr and Phillips 1999;Corrigall et al 1989;LeSage et al 2006) and monkeys (Carroll 1987;Carroll and Carmona 1991;Perry et al 2006). Disruption in behavior maintained by nondrug substances occurred during withdrawal from several drugs (e.g., amphetamine, nicotine, phencyclidine (PCP)) and after short access to the drug when no other physical signs of drug withdrawal were apparent (e.g., Carroll 1987;Carroll and Carmona 1991;Perry et al 2006). The term withdrawal is used here to refer to the procedure of removing drug access and the mild behavioral disruptions that may represent a subtle form of physical dependence.…”

Impulsivity (delay discounting) for food and cocaine in male and female rats selectively bred for high and low saccharin intake

“…Similarly, HiS rats outperform LoS rats under many of the same drug-related conditions, such as acquisition , escalation (Perry et al, 2006a), and reinstatement (Perry et al, 2006a) of drug-seeking behavior. Interestingly, one area where males show a greater drug effect than females is in disruptions in operant behavior during drug withdrawal (Perry et al, 2006b), and recent evidence suggests that LoS rats also exceed HiS rats in their behavioral suppression during drug withdrawal (Dess et al, 2005). The literature and the present results emphasize the salience of selective breeding for saccharin intake and sex as factors that influence vulnerability to drug abuse.…”

Effects of menstrual cycle phase on the reinforcing effects of phencyclidine (PCP) in rhesus monkeys

“…Sex differences have been demonstrated in behavioral dependence upon on orally self-administered PCP. Perry et al (2006) found that males exhibit a stronger and more prolonged disruption in food-maintained behavior after withdrawal from PCP than females.…”