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

Exp Clin Psychopharmacol. 2006 Feb;14(1):68-78. doi: 10.1037/1064-1297.14.1.68.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Female
  • Macaca mulatta
  • Male
  • Phencyclidine / administration & dosage*
  • Phencyclidine / pharmacokinetics
  • Reinforcement Schedule
  • Self Administration
  • Sex Characteristics*
  • Substance Withdrawal Syndrome / etiology
  • Substance-Related Disorders / etiology*


  • Phencyclidine