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 circadian rhythms, impaired locomotor activity, and reflexes, as well as decreased threshold to noxious stimuli. In addition, following portacaval shunting, rats drink significantly more ethanol in a free-choice drinking paradigm. Available evidence suggests that many of these behavioral changes may be modulated by the endogenous opioid system of the brain. To evaluate this possibility, the effects of PCA on circulating beta-endorphin (beta-EP), as well as beta-EP content in the pituitary and specific brain nuclei, was evaluated using a sensitive radioimmunoassay. Furthermore, the characteristics and regional densities of mu and delta opioid receptors in the brains of PCA and sham-operated control rats were studied using an in vitro technique, as well as quantitative receptor autoradiography and the specific ligands 125I [D-Ala2, MePhe4, Met(o)ol5]enkephalin (FK 33-824) and 125I [2-D-penicillamine, 5-D-penicillamine]-enkephalin (DPDPE) for micro and delta sites, respectively. PCA resulted in region-selective modifications of beta-EP in brain, but not in pituitary or blood. Autoradiographic studies revealed a generalized decrease in mu binding sites (up to 70% decreases compared with sham-operated controls) and region-selective alterations of delta receptor densities following PCA. Portacaval-shunted rats drank 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 appeared to result from modifications of the endogenous opioid system in nucleus accumbens of rats following PCA.
de Waele
J P
JP
Neuroscience Research Unit, André-Viallet Clinical Research Center, Hôpital Saint-Luc, Université de Montréal, Québec, Canada.
Audet
R M
RM
Leong
D K
DK
Butterworth
R F
RF
D000428:Alcohol Drinking; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010902:Pituitary Gland / Q000378:metabolism; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D001615:beta-Endorphin / Q000032:analysis / Q000378:metabolism*
D004745:Enkephalins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D001615:beta-Endorphin; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D020881:Enkephalin, D-Penicillamine (2,5)-