Short- and Long-Term Cognitive Effects of Chronic Cannabinoids Administration in Late-Adolescence Rats

Hila Abush,Irit Akirav,Masabumi Minami

doi:10.1371/journal.pone.0031731

Hila Abush, Irit Akirav + Show 1 more

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https://doi.org/10.1371/journal.pone.0031731

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Journal: PloS one	Publication Date: Feb 13, 2012
Citations: 179	License type: CC BY 4.0

Affiliation: University of Haifa

Abstract

The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg) for two weeks during the late adolescence period (post-natal days 45–60) and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

Highlights

Cannabis is the most widely used illicit drug after nicotine and alcohol [1] and can impair several aspects of cognitive function [2,3].In humans, cannabinoids impair both encoding and recall of verbal and non verbal information depending on dose and task difficulty [2]
Given the well established role of the hippocampus in learning and memory processes, and its high expression of CB1 receptors [5,6], it is likely that the adverse effects of cannabinoids on spatial learning tasks, short-term memory, and attention are attributable to their actions within this brain region
Using electrophysiological recordings from hippocampal slices, previous studies have shown that cannabinoid receptor activation inhibits long-term potentiation (LTP) in the hippocampus [7,8,9,10,11]

Summary

Introduction

Cannabis is the most widely used illicit drug after nicotine and alcohol [1] and can impair several aspects of cognitive function [2,3].In humans, cannabinoids impair both encoding and recall of verbal and non verbal information depending on dose and task difficulty [2]. Cannabinoids impair memory in a variety of experimental conditions such as the radial maze, instrumental discrimination tasks and the Morris water maze [4]. Using electrophysiological recordings from hippocampal slices, previous studies have shown that cannabinoid receptor activation inhibits LTP in the hippocampus [7,8,9,10,11]. WIN administered systemically or into the CA1 (5 mg/side) impairs spatial learning in the water maze [12]. Acute exposure to cannabinoids impairs both hippocampal spatial learning and LTP. We found that acute WIN administered into the ventral subiculum (vSub; 5 mg/side) impairs acquisition and retrieval of memory in the social discrimination task [13]

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