Biphasic effects of Δ9-tetrahydrocannabinol on brain stimulation reward and motor activity

Abstract

Abstract Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive ingredient of marijuana, has led to equivocal results when tested with the intracranial self-stimulation (ICSS) procedure or the open-field test for motor activity, two behavioural models for evaluating the reward-facilitating and locomotor stimulating effects of drugs of abuse, respectively. Therefore, in the present study, the effects of high and low doses of Δ9-THC were compared in the ICSS procedure and the open-field test. Moreover, the involvement of CB1 receptors in tentative Δ9-THC-induced effects was investigated by pre-treating the animals with the CB1 receptor antagonist SR141716A (rimonabant). The results obtained show that low doses of Δ9-THC induce opposite effects from high doses of Δ9-THC. Specifically, 0.1 mg/kg Δ9-THC decreased ICSS thresholds and produced hyperactivity, whereas 1 mg/kg increased ICSS thresholds and produced hypoactivity. Both effects were reversed by pre-treatment with SR141716A, indicating the involvement of CB1 receptors on these actions. Altogether, our results indicate that Δ9-THC can produce acute activating effects in locomotion that coincide with its reward-facilitating effects in the ICSS paradigm. The present findings provide further support that Δ9-THC induces behaviours typical of abuse and substantiate the notion that marijuana resembles other drugs of abuse.