DOPAMINE IN THE MESOLIMBIC SYSTEM OF THE RAT BRAIN: ENDOGENOUS LEVELS AND THE EFFECTS OF DRUGS ON THE UPTAKE MECHANISM AND STIMULATION OF ADENYLATE CYCLASE ACTIVITY

Abstract

Abstract— High concentrations of dopamine were found in the nucleus accumbens and olfactory tubercle of the rat brain using a radiochemical enzymatic assay technique. An active uptake system for [ 3 H]dopamine that is temperature sensitive and dependent on external sodium ions is present in synaptosome‐rich homogenates of these two brain areas. This uptake process is potently inhibited by benztropine (IC 50 = 2.0 × 10 ‐7 m ). Dextroamphetamine d was 4.5 times more potent than 1‐amphetamine in inhibiting dopamine uptake in the nucleus accumbens and six times more potent in the olfactory tubercle and corpus striatum . Low concentrations of dopamine caused an increase in adenosine 3′5′‐monophosphate (cyclic AMP) formation in homogenates of both the nucleus accembens and olfactory tubercle. This effect was potently blocked by chlorpromazine. The α‐adrenoceptor antagonist phentolamine weakly antagonized the stimulation of this adenylate cyclase by dopamine, but the β‐adrenoceptor antagonist propranolol did not.