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 agon ists induces sedation and immobility [1,5], and attenuates the behavio ural activation produced by the dopamine D-2 agonist quinpirole [5]. I n contrast, kappa-selective opioid agonists induce dystonic-like movem ents [4,5,8]. This has led us to investigate the possibility of an int eraction between acute opioid treatment and the dopamine D-2 system. T he 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 mor phine (15 mg/kg subcutaneously, SC) given for 2 h, and the delta recep tor selective agonist DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen) (20 nM, intracer ebroventricularly, ICV) given for 0.5 h, both decreased the density of specific (butaclamol displaceable) [H-3]spiperone binding in the caud ate putamen by 23.8 +/- 1.7% and 24.2 +/- 2.7% respectively, and in nu cleus accumbens by 26.1 +/- 2.7% and 21.9 +/- 4.6% respectively compar ed to saline treated animals. There were no significant changes in the level of [H-3]spiperone binding to other brain regions examined inclu ding frontal cortex, hippocampus, substantia nigra, ventral tegmental area, amygdala, hypothalamic nuclei and cerebellum In other experiment s, incubation of coronal slices from various brain regions with [H-3]s piperone, 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 preclud ing effects due to residual tissue levels of drugs after in vivo treat ment. The kappa-selective agonist U59,488H ns-(+/-)-3,4-dichloro-N-met hyl-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methane sulphonat e) (10 mg/kg, SC) given for 1 h, had no significant effect on the dens ity of [H-3]spiperone binding in the various guinea-pig brain regions. It is concluded that acute treatment with mu and delta opioid agonist s may downregulate dopamine D-2 receptors in striatum and nucleus accu mbens. Such an action may partly explain the attenuation of the behavi oural response produced by the dopamine D-2 agonist quinpirole as demo nstrated in our previous study [5].