The effects of tifluadom and ketazocine on behaviour, dopamine turnover in the basal ganglia and local cerebral glucose utilization of rats.

The purpose of the present study was to evaluate the interrelation between behavioural effects of kappa-opiates and cerebral neurochemical correlates in rats. Administration of the kappa-opiates tifluadom (2.5 mg/kg i.p.) or ketazocine (5 mg/kg i.p.) caused a marked initial decrease in locomotor activity lasting about 15-20 min, followed by an increase in locomotor activity at about 40 min after drug administration. At 15 min after i.p. injections of the same drugs 3,4-dihydroxyphenylacetic acid concentrations, measured by HPLC, were slightly increased in the nucleus accumbens, but unchanged in the striatum; dopamine concentrations were unchanged in both regions. The rates of glucose utilization, determined by quantitative [14C]2-deoxyglucose autoradiography, were mainly unchanged except for the nucleus accumbens, which showed an increased glucose utilization after both drugs given i.v. Tifluadom also decreased rates of glucose utilization in the caudate nucleus and parietal, sensorimotor, olfactory and frontal cortices. The above-mentioned effects on behaviour and local cerebral glucose utilization could be prevented by naloxone (3 mg/kg). The data suggest that changes in locomotor activity, neurotransmitter metabolism and neuronal activity in the nucleus accumbens are interrelated and that opiate-induced akinesia is mediated via the nucleus accumbens.