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Memory impairment following combined exposure to delta(9)-tetrahydrocannabinol and ethanol in rats.

Roberto Ciccocioppo, Lorena Antonelli, Michela Biondini, Marina Perfumi, Pierluigi Pompei, Maurizio Massi

European Journal of Pharmacology August 9, 2002 DOI: 10.1016/s0014-2999(02)01999-4 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled experimental animal study Peer reviewed
Population Alcohol-preferring rats
Interventions delta(9)-tetrahydrocannabinol (THC) SR 141716A
Dose THC 2, 5, or 10 mg/kg; SR 141716A 1 mg/kg
Measures object recognition test
Topics Cannabis
Key findings Ethanol ingested voluntarily by alcohol-preferring rats and intraperitoneal THC acted synergistically to impair object recognition at a 15-minute delay: neither ethanol alone nor 2 or 5 mg/kg THC alone changed performance, but their combination markedly impaired it, while THC alone impaired recognition only at 10 mg/kg. The CB(1) antagonist SR 141716A (1 mg/kg) reversed the 10 mg/kg THC effect, and the synergy was absent at a 1-minute inter-trial interval.

Abstract

Cannabis derivatives and alcohol are widely co-abused, particularly among adolescents. Since both ethanol and cannabinoids are known to impair learning and memory, the present study investigated in rats the effects of combined exposure to ethanol and delta(9)-tetrahydrocannabinol (THC) in a memory task, the object recognition test. The results of the present study provide evidence that ethanol, voluntarily ingested in alcohol-preferring rats, and THC, given by intraperitoneal injection, have a synergic action to impair object recognition, when a 15-min interval was adopted between the sample phase and the choice phase of the test. Neither voluntary ethanol ingestion nor 2 or 5 mg/kg of THC were able per se to modify object recognition in these experimental conditions, but when voluntary ethanol ingestion was combined with administration of these doses of THC object recognition was markedly impaired. THC impaired object recognition only at the dose of 10 mg/kg, when its administration was not combined with that of ethanol. The selective cannabinoid CB(1) receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1(2, 4-dichloro-phenyl)-4-methyl-1H-pyrazole carboxamide.HCl) at the dose of 1 mg/kg reversed the amnesic effect of THC, 10 mg/kg, suggesting that the effect is mediated by this receptor subtype. The synergism of ethanol and THC was not detected when an inter-trial interval of 1 min was adopted. The present findings are in keeping with the notion that Cannabis derivatives impair memory processes and provide evidence for a synergic action of THC and ethanol, thus emphasizing the risks consequent to their co-administration.

Comparable studies

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Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
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Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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