The effect of chronic ethanol consumption and withdrawal on mu-opioid and dopamine D(1) and D(2) receptor density in Fawn-Hooded rat brain.
Previous studies have implicated the dopamine and opioid systems in the induction and maintenance of ethanol consumption. This study investigated, in alcohol-preferring Fawn-Hooded (FH) rats, whether chronic free-choice ethanol consumption and subsequent withdrawal cause alterations in central mu-opioid, dopamine D(1), and D(2) receptor density using autoradiography. FH rats were given a free choice between a 5% ethanol solution and tap water (n = 25) and displayed a mean ethanol consumption of 5.6 g/kg/day. A parallel group of FH rats (n = 5) only had access to tap water. Rats were then withdrawn from ethanol for 0, 1, 2, 5, or 10 days and killed by cervical dislocation and decapitation. Increases in mu-opioid receptor density were observed in the nucleus accumbens and ventral tegmental area upon withdrawal compared with the ethanol naive group. In the lateral amygdala, binding in all withdrawal groups was significantly different from the ethanol naive FH rats, and also from the chronic ethanol rats. An increase in dopamine D(1) receptor density was observed in the substantia nigra, pars reticulata in the 5- and 10-day withdrawal groups compared with ethanol naive. Accumbal dopamine D(2) receptor density (+25-30%) increased in the 10-day withdrawal group compared with both naive and chronic ethanol groups. These findings demonstrate that the opioid and dopamine systems are susceptible to modulation by chronic ethanol consumption and withdrawal in the FH rat. Furthermore, although acute ethanol withdrawal results in modulation of mu-opioid receptors, effects on dopamine receptors are delayed and only become evident 5 to 10 days after withdrawal.
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Elvan
E
Djouma
Andrew J
AJ
Lawrence
D000428:Alcohol Drinking / Q000378:metabolism*; D000430:Alcohol Withdrawal Delirium / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D004327:Drinking Behavior; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D007457:Iodine Radioisotopes; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu