PORTACAVAL ANASTOMOSIS INDUCES REGION-SELECTIVE ALTERATIONS OF THE ENDOGENOUS OPIOID SYSTEM IN THE RAT-BRAIN

Portacaval anastomosis (PCA) in the rat results in a broad spectrum of neurological and neurobehavioral changes, including alterations of ci rcadian rhythms, impaired locomotor activity, and reflexes, as well as decreased threshold to noxious stimuli. In addition, following portac aval shunting, rats drink significantly more ethanol in a free-choice drinking paradigm. Available evidence suggests that many of these beha vioral changes may be modulated by the endogenous opioid system of the brain. To evaluate this possibility, the effects of PCA on circulatin g beta-endorphin (beta-EP), as well as beta-EP content in the pituitar y and specific brain nuclei, was evaluated using a sensitive radioimmu noassay. Furthermore, the characteristics and regional densities of mu and delta opioid receptors in the brains of PCA and sham-operated con trol rats were studied using an in vitro technique, as well as quantit ative receptor autoradiography and the specific Ligands I-125 [D-Ala(2 ), MePhe(4), Met(o)ol(5)]enkephalin (FK 33-824) and I-125 [2-D-penicil lamine, 5-D-penicillamine]-enkephalin (DPDPE) for mu and delta sites, respectively. PCA resulted in region-selective modifications of beta-E P in brain, but not in pituitary or blood. Autoradiographic studies re vealed a generalized decrease in mu binding sites (up to 70% decreases compared with sham-operated controls) and region-selective alteration s of delta receptor densities following PCA. Portacaval-shunted rats d rank significantly more ethanol in a free-choice drinking paradigm, an effect that was significantly attenuated by the administration of the opiate antagonist naloxone. Increased ethanol preference thus appeare d to result from modifications of the endogenous opioid system in nucl eus accumbens of rats following PCA.