THE ROLE OF NUCLEUS-ACCUMBENS DOPAMINE IN THE NEUROCHEMICAL AND BEHAVIORAL-EFFECTS OF PHENCYCLIDINE - A MICRODIALYSIS AND BEHAVIORAL-STUDY

A series of experiments were conducted in order to characterize the role of nucleus accumbens dopamine (DA) in the neurochemical and behavioral effects of phencyclidine (PCP). In the first study, microdialysis probes were implanted in nucleus accumbens to determine the effects of 4.0 and 8.0 mg/kg PCP on extracellular levels of DA and its metabolites, dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) in behaving rats. PCP increased extracellular DA, DOPAC and HVA in the same dose range that produced increases in locomotor activity, stereotypy and ataxia. The increases in extracellular DA that were induced by 4.0 mg/kg PCP were significantly correlated with the increases in locomotor activity. In the second study, rats received bilateral injections of 6-hydroxydopamine in order to deplete DA in nucleus accumbens. DA-depleted and control rats received injections of saline and 4.0 mg/kg PCP and were tested in an 'intruder' paradigm. In this procedure, saline- and PCP-treated rats were placed in a stable colony of three other rats and social behavior was observed for 30 min. PCP reduced the frequencies of various social behaviors, but accumbens DA depletion did not reverse the effects of PCP on social behavior. Subsequently, all rats received 8.0 mg/kg PCP and were assessed for locomotor activity, stereotypy and ataxia. Depletion of DA in nucleus accumbens attenuated PCP-induced locomotion, but did not alter the effects of the drug on stereotypy or ataxia. These results indicate that DA in nucleus accumbens is related to the locomotor effects of PCP, but that the effects of PCP on social behavior, stereotypy and ataxia are dependent upon DA in other brain regions or on neurotransmitters other than DA.