SHORT AND LONG-TERM CHANGES IN DOPAMINE AND SEROTONIN RECEPTOR-BINDING SITES IN AMPHETAMINE-SENSITIZED RATS - A QUANTITATIVE AUTORADIOGRAPHIC STUDY

The biochemical changes in DA and 5HT systems were investigated in amp hetamine (AMPH)-sensitized rats, 1 and 15 days after cessation of trea tment (5 mg/kg AMPH, i.p., twice a day for 6 days). At both times, AMP H-treated rats exhibited behavioral sensitization, as revealed by an e nhancement of the stereotypic response to a challenge dose of 2 mg/Kg, ip. AMPH. Basal dopamine (DA) and serotonin (5-HT) metabolism was not significantly modified in different brain areas of AMPH-sensitized ra ts. Quantitative autoradiographic analysis of DA and serotonin 5-HT re ceptor subtypes was performed in the following brain regions: medial p refrontal cortex, nucleus accumbens,striatum, substantia nigra, ventra l tegmental area, dorsal and median raphe nuclei. A significant increa se of [H-3]SCH 23390 binding to D-1 DA receptors was observed in the s ubstantia nigra pars reticulata 1 day but not 15 days after the cessat ion of AMPH treatement, whereas [H-3]8-OH-DPAT binding to 5-HT1A sites was found to be significantly enhanced in the dorsal raphe nucleus at both time points. No change in D-1 DA nor in 5-HT1B or 5-HT2A recepto rs was found in any of the brain structures examined at either time po int. The obtained results suggest that DA and 5-HT systems are differe ntly and time-dependently involved in AMPH-induced behavioral sensitiz ation.