Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration.
Angelica Rocha, Nigel Hart, Keith A Trujillo
Pharmacology, Biochemistry, and Behavior June 1, 2017 DOI: 10.1016/j.pbb.2017.04.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Periadolescent and adult Sprague-Dawley rats |
| Interventions | PCP ketamine |
| Dose | 6 mg/kg IP for PCP, 20 mg/kg IP for ketamine |
| Duration | Five injections once every three days |
| Topics | Addiction Ketamine Esketamine |
| Keywords | Locomotor Phencyclidine Sensitization |
| Key findings | Adolescent rats show a greater acute stimulant response to PCP and ketamine than adults, but adults develop stronger sensitization with repeated doses. |
Abstract
Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine.
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 |
Citations in the library
Cited by 16
- The abuse liability of ketamine: A scoping review of preclinical and clinical studies. Journal of Psychiatric Research May 1, 2022
- Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review Frontiers in Neuroanatomy March 18, 2022
- Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs Frontiers in Psychiatry August 18, 2017
- On the safety of repeated ketamine infusions for the treatment of depression: Effects of sex and developmental periods Neurobiology of Stress September 21, 2018
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
and 11 more in the library
Cites 11
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- A Review of the Nonmedical Use of Ketamine: Use, Users and Consequences Journal of Psychoactive Drugs December 1, 2000
- Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. European Journal of Pharmacology March 3, 1987
- Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia Journal of Psychiatric Research December 24, 2014
- Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade Frontiers in Molecular Neuroscience September 11, 2015
and 6 more in the library