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Updated: Aug 19, 2026

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Alpha-noradrenergic receptor modulation of the phencyclidine- and delta9-tetrahydrocannabinol-induced increases in
1Neuropsychopharmacology Research Unit, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.
Abstract:
The noncompetitive NMDA receptor antagonist phencyclidine (PCP) and the neuronal cannabinoid receptor agonist delta9-tetrahydrocannabinol (THC) are two agents shown to have psychotomimetic properties in humans. Both drugs increase dopamine release and utilization in the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. In the present series of studies, the effects of drugs acting at alpha-noradrenergic receptors on PCP- and THC-induced increases in prefrontal cortical and nucleus accumbens dopamine utilization in the rat were examined. Clonidine, an alpha2 noradrenergic receptor agonist, completely blocked the activation of mesoprefrontal dopamine system by THC or PCP. In addition, the alpha1 noradrenergic receptor antagonist prazosin blocked the PCP-induced increase in prefrontal cortical dopamine utilization. These data may provide new insights concerning pharmacological therapies for acute drug-induced psychoses and behavioral abnormalities in human PCP and THC abusers.
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