This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D 2/3 R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D 2/3 R levels in striatum, as assessed using [3H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D 2/3 R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [3H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation. Parallel analyses of the psychomotor effects of pre- and post-synaptic doses of quinpirole also showed a pattern of D 2/3 R functional supersensitivity indicative of more rapid subsidence in striatum than in midbrain following drug cessation. These results indicate that chronic THC is associated with a biochemical and functional sensitization of D 2/3 R signaling, that these responses show a region-specific temporal pattern and are fully reversible following drug discontinuation. These results suggest that an increased post-synaptic D 2/3 R function and a decreased DA presynaptic signaling, mediated by increased D 2/3 R autoinhibition, may predominate during distinct phases of withdrawal and may contribute both to the mechanisms leading to relapse and to cannabinoid withdrawal symptoms. The different rates of normalization of D 2/3 R function in striatum and midbrain may be critical information for the development of new pharmacotherapies for cannabis dependence.