Separate measures of ethanol seeking and drinking in the rat: effects of remoxipride.
Remoxipride, a dopamine D(2) antagonist, decreases responding that results in the presentation of small amounts (approximately 0.1 ml) of ethanol in limited-access paradigms. This type of operant response is a combined appetitive/consummatory response that is differentially affected by changing stimulus properties of consumed ethanol (i.e., taste, pharmacology) over the course of the session. In the present experimental design, ethanol-directed appetitive and consummatory responses were procedurally separated to investigate the specific effects of remoxipride on these distinct behaviors. Male Long-Evans rats were trained to make a series of lever-press responses once each day that resulted in access to a sipper tube spout containing 10% ethanol for 20 min. Three doses of remoxipride were tested: 5.0, 10.0, and 15.0 mg/kg (-30 min, i.p.). In Experiment 1, a response requirement of 20 was used, and both reinforced and nonreinforced sessions were examined. In nonreinforced sessions, subjects were permitted to lever press for 20 min, after which the session ended without sipper tube presentation. These sessions were conducted to remove the possibility that limiting responding might obscure a drug effect on the seeking response. In Experiment 2, a low response requirement (4) was used to investigate the effects of remoxipride on ethanol intake. Average baseline ethanol intake (Experiment 1) was 0.69 g/kg, with blood ethanol concentrations at the end of the session at 64 mg%. At all doses tested, remoxipride had no effect on the measures of ethanol consumption (e.g., total intake, lick latency, lick rate) in either experiment. However, remoxipride dose dependently decreased the number of appetitive responses made, while having no effect on response latency or rate, during both reinforced and nonreinforced sessions in Experiment 1. In these experiments, the systemic antagonism of the dopamine D(2) receptor decreased ethanol seeking without causing a general impairment of motor function. The procedural separation of seeking and intake responses revealed that appetitive responding was more sensitive than consummatory responding to remoxipride treatment.
Czachowski
Cristine L
CL
Department of Physiology and Pharmacology, Center for the Neurobehavioral Study of Alcohol, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. cczachow@wfubmc.edu
Santini
Lindsay A
LA
Legg
Brooke H
BH
Samson
Herman H
HH
D000428:Alcohol Drinking / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D016739:Behavior, Addictive / Q000097:blood / Q000188:drug therapy*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012054:Reinforcement, Psychology; D017330:Remoxipride / Q000494:pharmacology / Q000627:therapeutic use*
D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D017330:Remoxipride