Neurochemical and behavioural correlates of the interaction between amphetamine and Δ9-tetrahydrocannabinol in the rat

Abstract

A single dose of Δ 9-tetrahydrocannabinol (THC) (10 or 100 mg/kg) was administered via stomach gavage following the single injection intraperitoneally of an acute dose of amphetamine (1 or 3 mg/kg) in the rat. The THC effects, which included a reduction in spontaneous locomotor activity, the development of prostration, and circling behaviour, were antagonized in a dose-dependent manner by pretreatment with amphetamine. Although no change in the endogenous levels of noradrenaline, dopamine and serotonin in hypothalamus, hippocampus, caudate-putamen or the rest of brain occurred with THC, it appears that THC may have increased dopamine turnover in the brain. The dose-dependent amphetamine antagonism to the behavioural effects of THC was paralleled by a dose-related increase in brain dopamine concentration. This elevation in dopamine levels may be instrumental in triggering the neuronal events responsible for the amphetamine antagonism of the actions of THC. The subtle interaction of THC with brain dopamine neural systems may be involved in the reinforcing properties of the self-administration of THC.