Chronic D1 agonist and ethanol coadministration facilitate ethanol-mediated behaviors.
Separate lines of evidence suggest that neuroadaptations associated with ethanol (EtOH) reinforcement can be initiated by chronic EtOH preexposure and a signaling pathway activated by dopamine (DA) D1 receptor stimulation. We have previously shown that rewarding and locomotor effects of EtOH alone [Pharmacol. Biochem. Behav. 72 (2002) 787] are enhanced after chronic exposure to self-administered EtOH/cocaine combinations. To determine the importance of chronic EtOH exposure, dopamine D1 receptor activation and mode of drug administration in EtOH reward, animals were given daily intravenous infusions of experimenter-administered saline, EtOH (2.0 g/kg), the DA D1 receptor agonist, SKF81297 (0.2 mg/kg), or EtOH+SKF81297 over a 4-week period. Compared to other groups, animals preexposed to EtOH+SKF81297 self-administered significantly greater amounts of intravenous EtOH and showed greater enhancement and less suppression of locomotor activity in response to a range of intravenous EtOH dosages (0.125, 0.25, 0.5, 1.0 and 1.5 g/kg). Since chronic treatment with EtOH alone did not enhance EtOH-induced reinforcement or locomotor activity, it is unlikely that these effects were due to EtOH tolerance. These findings suggest that chronic D1 receptor activation combined with EtOH administration alters neural responsiveness to EtOH and support the notion that D1 activation is important to EtOH reward.
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, 1 University Station A1915, Austin, TX 78712-0125, USA.
Manoranjan S
MS
D'Souza
Aiko
A
Ikegami
Christopher M
CM
Olsen
Christine L
CL
Duvauchelle
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005502:Food; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D012054:Reinforcement, Psychology; D012646:Self Administration
D001552:Benzazepines; D002492:Central Nervous System Depressants; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D000431:Ethanol; C067113:SK&F 81297