Aversive effects of the synthetic cannabinoid CP 55,940 in rats

doi:10.1016/0091-3057(95)02066-7

Pharmacology Biochemistry and Behavior

Volume 53, Issue 3, March 1996, Pages 657-664

https://doi.org/10.1016/0091-3057(95)02066-7 Get rights and content

Abstract

A series of experiments investigated the behavioral and hedonic effects of the synthetic cannabinoid CP 55,940 in male Wistar rats. CP 55,940 had a biphasic effect on locomotor activity, with a 10 μg/kg dose causing locomotor stimulation and a 100 μg/kg dose causing profound hypoactivity. CP 55,940 (100 μg/kg) also caused a marked hypothermia for at least 3 h following administration, while lower doses (2.5 and 10 μg/kg) had no effect. CP 55,940 (100 gmg/kg) had anorexic and hyperdipsic effects for up to 24 h following administration and caused significant reductions in body weight. CP 55,940 (100 μg/kg) also caused significant avoidance to a flavoured fluid (saccharin) with which it was paired. In the conditioned place preference paradigm both the 10 μg/kg and 100 μg/kg doses of CP 55,940 produced significant place avoidance. It is concluded that CP 55,940 is aversive to rats. The possible mechanisms underlying this aversion are discussed.

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Previous reports on cannabinoids demonstrated that any slight modification in the CPP procedure might produce a dramatic shift in CPP outcomes [for review, see Ref. [63]. For example, aversive effects were reported when CP was administered daily for four days in conditioning training [51], which could account for the failure to observe a positive CPP effect. Moreover, the narrow interval between cannabinoids injections can produce a similar dysphoric effect on the brain’s reward threshold, which may mask the rewarding effect, as proposed in previous report [53].
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Subjects assigned to the norBNI group were injected subcutaneously (SC) with norBNI (15 mg/kg) 24 h prior to place conditioning; subjects assigned to the Vehicle group were injected SC with the norBNI vehicle. Given that THC typically produces a conditioned place aversion in rats (Mallet and Beninger, 1998; McGregor et al., 1996; Parker and Gillies, 1995; Sañudo-Peña et al., 1997), each animal was given THC on its own initially preferred side (for similar procedures with drugs that typically induce place aversions, see Cunningham et al., 2003; Davis et al., 2007; Schenk et al., 1986). Specifically, 24 h after norBNI/vehicle administration (see above), animals in each pretreatment group were randomly assigned to receive an intraperitoneal (IP) injection of THC (0, 0.56, 1 or 3.2 mg/kg).
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In Experiment 1, THC produced dose-dependent place aversions that were unaffected by norBNI (15 mg/kg). In Experiment 2, THC induced significant place aversions that were fully attenuated by norBNI (30 mg/kg).
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ArticleAversive effects of the synthetic cannabinoid CP 55,940 in rats

Abstract

Prog. Neuropsychopharmacol. Biol. Psychiatry

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Physiol. Behav.

Learn. Motiv.

Toxicol. Appl. Pharmacol.

Brain Res.

Blockade of acquisition of drug-conditioned place aversion by 5-HT3 antagonists

Psychopharmacology (Berlin)

Adverse reactions and recurrences from marijuana use

Br. J. Addict.

Marijuana as medicine

Med. J. Aust.

Reinforcing and subjective effects of oral Δ9THC and smoked marijuana in humans

Psychopharmacology (Berlin)

Reluctance of rats to drink hashish suspensions: Free-choice and forced consumption, and the effects of hypothalamic stimulation

Psychopharmacologia

Isolation and structure of a brain constituent that binds to the cannabinoid receptor

Science

Δ9-Tetrahydrocannabinol: Aversive effects in rat at high doses

Science

Changes in body temperature and oxygen consumption rate of conscious mice produced by intrahypothalamic and intracerebroventricular injection of Δ9-tetrahydrocannabinol

Eur. J. Pharmacol.

Article
Aversive effects of the synthetic cannabinoid CP 55,940 in rats

Blockade of acquisition of drug-conditioned place aversion by 5-HT₃ antagonists

Reinforcing and subjective effects of oral Δ⁹THC and smoked marijuana in humans

Δ⁹-Tetrahydrocannabinol: Aversive effects in rat at high doses

Changes in body temperature and oxygen consumption rate of conscious mice produced by intrahypothalamic and intracerebroventricular injection of Δ⁹-tetrahydrocannabinol