IN-VIVO TREATMENT WITH MU-SELECTIVE AND DELTA-SELECTIVE, BUT NOT KAPPA-SELECTIVE OPIOID AGONISTS REDUCES [H-3] SPIPERONE BINDING TO THE GUINEA-PIG STRIATUM - AUTORADIOGRAPHIC EVIDENCE

In guinea-pigs, acute treatment with mu and delta receptor opioid agonists induces sedation and immobility [1,5], and attenuates the behavioural activation produced by the dopamine D-2 agonist quinpirole [5]. In contrast, kappa-selective opioid agonists induce dystonic-like movements [4,5,8]. This has led us to investigate the possibility of an interaction between acute opioid treatment and the dopamine D-2 system. The effect of acute treatment with mu, delta and kappa opioid agonists on [H-3]spiperone binding sites (dopamine D-2) in guinea-pig brain was studied using receptor autoradiography. The mu preferring agonist morphine (15 mg/kg subcutaneously, SC) given for 2 h, and the delta receptor selective agonist DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen) (20 nM, intracerebroventricularly, ICV) given for 0.5 h, both decreased the density of specific (butaclamol displaceable) [H-3]spiperone binding in the caudate putamen by 23.8 +/- 1.7% and 24.2 +/- 2.7% respectively, and in nucleus accumbens by 26.1 +/- 2.7% and 21.9 +/- 4.6% respectively compared to saline treated animals. There were no significant changes in the level of [H-3]spiperone binding to other brain regions examined including frontal cortex, hippocampus, substantia nigra, ventral tegmental area, amygdala, hypothalamic nuclei and cerebellum In other experiments, incubation of coronal slices from various brain regions with [H-3]spiperone, in the presence of a high concentration of morphine (20 mu M) or DPDPE (10 mu M) did not affect the level of binding, thus precluding effects due to residual tissue levels of drugs after in vivo treatment. The kappa-selective agonist U59,488H (trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methane sulphonate) (10 mg/kg, SC) given for 1 h, had no significant effect on the density of [H-3]spiperone binding in the various guinea-pig brain regions. It is concluded that acute treatment with mu and delta opioid agonists may downregulate dopamine D-2 receptors in striatum and nucleus accumbens. Such an action may partly explain the attenuation of the behavioural response produced by the dopamine D-2 agonist quinpirole as demonstrated in our previous study [5].