Ethanol and sucrose seeking and consumption following repeated administration of the GABA(B) agonist baclofen in rats.

BACKGROUND: Baclofen, a GABA(B) agonist, has been found to decrease alcohol craving in humans and to nonselectively decrease ethanol intake in some rodent models. This experiment assessed the effects of repeated administration of baclofen on reinforcer seeking and consumption using the sipper tube appetitive/consummatory model of ethanol access. METHODS: Subjects were divided into 2 groups and trained to make 30 lever press responses that resulted in access to either 10% ethanol or 2% sucrose in a sipper tube-drinking spout for 20 minutes. Three doses of baclofen were tested (0.3, 1.0, and 3.0 mg/kg) and each drug treatment was assessed using the following schedule: Monday, saline; Tuesday to Thursday, baclofen; and Friday, saline. RESULTS: The low dose of baclofen had no effect on the seeking or intake of either sucrose or ethanol, and the 1.0 mg/kg dose also had no effect on the appetitive, seeking response. However, the 1.0 mg/kg dose significantly decreased sucrose intake (from an average of 0.56 to 0.41 g/kg) and significantly increased ethanol intake (from an average of 0.77 to 1.00 g/kg). Similarly, the high dose (3.0 mg/kg) decreased sucrose intake and had a tendency to increase ethanol intake while decreasing both sucrose seeking and ethanol seeking. CONCLUSIONS: Overall, baclofen treatment affected reinforcer intake at doses that had no effect on reinforcer seeking, and effective doses decreased both sucrose seeking and ethanol seeking. Moreover, the effects on reinforcer intake were disparate, in that baclofen increased ethanol drinking and decreased sucrose drinking. The nonspecific effects of baclofen suggest that the GABA(B) system may be involved in general consummatory or drinking behaviors and does not appear to specifically regulate ethanol-motivated responding.

Assessment of sucrose and ethanol reinforcement: the across-session breakpoint procedure.

We have demonstrated previously that the use of an across-session progressive ratio procedure yields breakpoint values for 10% ethanol (10E) that are stable and comparable to those measured for other drugs of abuse [Alcohol. Clin. Exp. Res. 23 (1999) 1580]. The aims of the present experiment were twofold: (1). to determine whether this procedure is sensitive to changes in reinforcer magnitude using a reinforcer previously demonstrated to affect operant responding in a predictable fashion and (2). to determine whether ethanol reinforcement produced similar changes in behavior. Male, Long-Evans rats were trained to respond for either 3% sucrose (3S) or 10E using the sipper tube appetitive/consummatory procedure where the completion of a single response requirement results in access to a liquid solution for 20 min. Three successive breakpoints were determined for this "baseline" solution by increasing the response requirement each day until it was not completed. The concentration of the solutions was then manipulated such that breakpoints for the Sucrose Group were assessed for 1%, 3%, 5% and 10% sucrose, and breakpoints for the Ethanol Group were assessed for 2%, 5%, 10% and 20% ethanol. The concentration manipulation showed that sucrose concentration had a greater impact on seeking and consumption than did ethanol concentration. Breakpoints in the Sucrose Group were highly correlated with sucrose concentration, whereas in the Ethanol Group, breakpoint was unrelated to ethanol concentration. Ethanol intake patterns suggested that pharmacological factors might have been regulating intake, and that when physiologically detectable amounts of ethanol were consumed, there was a dissociation between seeking and intake with slightly elevated ethanol seeking. Overall, the across-session breakpoint procedure confirmed that sweet taste was highly related to seeking and consumption, whereas ethanol-motivated responding may be controlled by different regulatory mechanisms that are distinct to seeking and consumption.

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.