Behavioral dependence upon phencyclidine and ketamine in the rat.
Patrick M. Beardsley, R. Balster
Journal of Pharmacology and Experimental Therapeutics July 1, 1987 DOI: 10.1016/s0022-3565(25)39053-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Rats |
| Interventions | Phencyclidine (PCP) Ketamine |
| Dose | 0.5 mg/kg/hr PCP; 2.5 mg/kg/hr ketamine |
| Duration | 10-day PCP infusion; withdrawal monitored within 6-12 hr onset and 24-48 hr recovery |
| Topics | Addiction Esketamine Ketamine |
| Key findings | Continuous intravenous infusion of PCP and ketamine induces dependence in rats, as evidenced by disrupted operant behavior during withdrawal, with cross-dependence from PCP to ketamine. |
Abstract
The present studies examined whether dependence could be induced by continuous i.v. infusion of phencyclidine (PCP) in rats as demonstrated by disruptions of operant behavior during withdrawal. Rats were trained to lever press for their daily food rations under fixed-ratio 30 schedules of reinforcement during four, daily, 0.5-hr sessions. In the first study, withdrawal from 10 days of PCP infusion at a rate of 0.5 mg/kg/hr resulted in markedly reduced response rates which typically occurred within 6 to 12 hr and recovered within 24 to 48 hr, providing evidence of dependence in the four rats tested. The PCP withdrawal effect was replicated systematically in seven additional rats which had been given individually maximally tolerated PCP infusion regimens. Additionally, when PCP was readministered during withdrawal, the downward trend in response rates was halted and rates increased rapidly to control levels, providing evidence of reversal of PCP withdrawal effects. When ketamine, another arylcyclohexylamine dissociative anesthetic, was administered during PCP withdrawal at a dose of 2.5 mg/kg/hr, it also was able to reverse PCP withdrawal effects, demonstrating cross-dependence from PCP to ketamine. Response rates were also reduced markedly relative to control levels during withdrawal from continuous i.v. ketamine infusion in three rats tested, providing evidence that dependence upon this drug could also be induced. Withdrawal of PCP and ketamine administration can disrupt operant behavior, providing further evidence for the ability of these drugs to produce dependence.
Comparable studies
Other preclinical and animal studies on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder. Morphine-dependent rats and mice | 2020 | Preclinical study | |
| The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Male and female oxycodone-dependent mice | 2023 | Preclinical study | |
| Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Adolescent rats of both sexes, including naïve and early-life stressed (maternal... | 2025 | Preclinical study | |
| Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. Long Evans rats | 2024 | Preclinical experimental study | |
| Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way. Male and female mice with forebrain ASM overexpression | 2025 | Experimental study |