Roles of dopamine D1 receptors in delta 9-tetrahydrocannabinol-induced expression of Fos protein in the rat brain.

We examined whether administration of delta 9-tetrahydrocannabinol (THC) induces the expression of Fos protein or not in the rat brain. A single administration of 3.2 and 10 mg/kg THC produced a dose-dependent and significant increase in Fos-immunoreactive cells in the striatum, particularly in its dorsomedial portions. The peak increase was reached 2 h after THC treatment and was absent at 8 h. Fos induction was also observed in the nucleus accumbens after administration of 10 mg/kg THC. However, in the globus pallidus, hippocampus and substantia nigra pars reticula, abundant in cannabinoid receptors, there were few or no Fos-immunoreactive cells induced by 10 mg/kg THC. SCH-23390, a selective dopamine D1 receptor antagonist, at 0.32 mg/kg produced a significant block of the effects of THC on Fos expression in the striatum and the nucleus accumbens. Administration of 100 mg/kg (-)-sulpiride, a selective dopamine D2 receptor antagonist, failed to block the effect of THC on Fos expression in both the striatum and the nucleus accumbens. These findings indicate that THC induces the expression of Fos protein and that this expression is mediated at least by dopamine D1 receptors.