EFFECT OF CONDITIONING WITH D-AMPHETAMINE ON THE EXTRACELLULAR CONCENTRATION OF DOPAMINE AND ITS METABOLITES IN THE STRIATUM OF BEHAVING RATS

The effect of classical conditioning with d-amphetamine on the extrace llular concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of awake, freely moving rats was studied using microdialysis. This was done in order to test, whether there occurred alterations in DA release as conditioned responses in the striatum. The first series of experiments studied th e acute effects of d-amphetamine on the concentration of DA and its me tabolites DOPAC and HVA. d-Amphetamine (2 mg/kg, s.c.) increased extra cellular DA and decreased DOPAC and HVA. Behaviorally, it led to stere otyped locomotor activation and sniffing. In principle, these observat ions confirmed earlier findings. In a second series, conditioned respo nses to d-amphetamine were studied. Rats were implanted with guide can nulas prior conditioning experiments started. For conditioning experim ents, the rats were divided into three groups: conditioned group, pseu doconditioned group and a drug-naive control group. After 7 daily trai ning sessions with d-amphetamine (2 mg/kg), on the 8th day, the test d ay, rats were injected with saline and exposed to the conditional stim uli, while they were observed for their stereotyped, conditioned respo nse. Additionally, microdialysis was performed in order to observe pos sible changes in the extracellular transmitter or metabolite concentra tions. Conditioning with amphetamine led to conditioned stereotypic be havior. In comparison with the pseudoconditioned rats, there was an in crease in DA release as conditioned response to amphetamine. In pseudo conditioned rats. DOPAC and HVA were slightly higher than in both othe r groups. DOPAC and HVA were lower in rats conditioned to d-amphetamin e when compared with the pseudoconditioned ones. The results suggest t hat with regard to DA release, the conditioned responses to d-amphetam ine mimicked the acute pharmacological responses. The same is valid fo r the DA metabolites, although in the opposite direction - they mimick ed decreases. Furthermore, the conditioned DA responses to d-amphetami ne might contribute to conditioned behavioral responses observed in th ese experiments.