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Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism.

Aron H Lichtman, B R Martin

Psychopharmacology July 1996 DOI: 10.1007/bf02246347 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical animal study Peer reviewed
Population Rats performing a radial-arm maze task
Interventions Delta 9-THC SR141716A scopolamine physostigmine
Topics Cannabis
Key points Delta 9-THC impaired radial-arm maze choice accuracy (ED50 = 3.0 mg/kg), and the cannabinoid antagonist SR141716A prevented this deficit dose-dependently (AD50 = 2.4 mg/kg). SR141716A did not improve scopolamine-induced deficits, and physostigmine did not improve delta 9-THC-induced deficits. The authors argue that delta 9-THC impairs working memory through direct cannabinoid receptor action and that scopolamine and delta 9-THC do not impair spatial memory via a common serial pathway, though they may converge on a third neurochemical system.

Abstract

The purpose of the present study was to investigate whether the cannabinoid and cholinergic systems impair working memory through a common mechanism. This hypothesis was tested by examining whether the cannabinoid antagonist SR141716A would ameliorate radial-arm performance deficits caused by either the naturally occurring cannabinoid, delta 9-THC, or scopolamine, a muscarinic antagonist. In addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would prevent delta 9-THC-induced impairment of spatial memory. Finally, because the locomotor suppressive effects of cannabinoids may decrease radial arm choice accuracy independent of a direct effect on memory, we examined the impact of increasing the intertrial error on radial arm choice accuracy. As previously reported, delta 9-THC impaired maze performance (ED50 = 3.0 mg/kg). Increasing the intertrial interval from 5 s to 30 s resulted in a three-fold increase in the amount of time required to complete the maze without affecting choice accuracy. Importantly, SR141716A prevented delta 9-THC-induced deficits in radial-arm choice accuracy in a dose-dependent manner (AD50 = 2.4 mg/kg); however, the cannabinoid antagonist failed to improve the disruptive effects of scopolamine. Conversely, physostigmine failed to improve performance deficits produced by delta 9-THC. These data provide strong evidence that delta 9-THC impairs working memory through direct action at cannabinoid receptors. Moreover, these results suggest that scopolamine and delta 9-THC do not impair spatial memory in a common serial pathway, though they may converge on a third neurochemical system.

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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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