Striatal dopamine receptors and adenylyl cyclase activity in a rat model of alcohol addiction: effects of ethanol and lisuride treatment.
In this report a novel animal model of spontaneous development of alcohol and drug addiction was used. Addiction to ethanol was induced in male Wistar rats (free choice between ethanol solutions and water for 11 mo). After 36 wk of alcohol deprivation these rats (series A) had ingested 3.4 +/- 0.4 g ethanol/kg/day. Age-matched, "controlled" alcohol consumers (series C: free choice for 8 wk) had ingested only 1.6 +/- 0.4 g/kg/day (P < .001). Two additional series of addicted (AL) and controlled alcohol-consuming rats (CL) received lisuride (90 micrograms/kg/day) for 8 wk concomitantly with the self-administered ethanol and again during the last week before death. Ethanol intake was increased by lisuride treatment in both groups (AL: 4.1 +/- 0.3 g/kg/day; CL: 2.7 +/- 0.4 g/kg/day; P < .05). Four months before death the alcohol was withdrawn. After this period of abstinence the in vitro dose-response curves for striatal dopamine D-1 receptor-stimulated adenylyl cyclase activity were determined (with eight concentrations of dopamine between 50 nM and 30 microM). Both lisuride-treated (AL) and untreated ethanol-addicted rats (A) displayed a significant (P < .01) increase in the effective concentration required to induce 50% of the response (EC50) as compared with controlled drinkers (C: 720 +/- 150 nM; A: 1820 +/- 390 nM; CL: 590 +/- 110 nM; AL: 1050 +/- 160 nM). Lisuride treatment increased forskolin- (10 microM) stimulated adenylyl cyclase activity and the Bmax of high-affinity [3H]DA binding to the D-1 site.(ABSTRACT TRUNCATED AT 250 WORDS)
May
T
T
Institut für Neuropsychopharmakologie, Freie Universität Berlin, Germany.
Wolf
U
U
Wolffgramm
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D008090:Lisuride / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D000431:Ethanol; D013134:Spiperone; D008090:Lisuride; D000262:Adenylyl Cyclases