BACKGROUND: Baclofen, a gamma-aminobutyric acid type B agonist, has been proposed as a pharmacotherapeutic agent in the treatment of addictive disorders such as alcoholism. Preclinical studies documenting the effect of baclofen on alcohol intake have provided conflicting results. The goal of this study was to determine the effect of baclofen pretreatment on ethanol- and sucrose-reinforced responding. METHODS: Animals were trained to self-administer a 10% ethanol in water solution on a fixed ratio 1 schedule of reinforcement by using the sucrose-fade method. With a within-subject design, the effect of three doses of baclofen (1.8, 3.2, and 5.6 mg/kg intraperitoneally) was examined on 10% ethanol- and 2% sucrose-reinforced responding. Dose-dependent effects on responding and on drinking-pattern microstructure were examined. RESULTS: Under a fixed ratio 1 schedule, baclofen reduced responding for alcohol and sucrose reinforcement in a similar, dose-dependent manner. A dose-dependent response attenuation was seen during the initial segment of an operant session when highly repetitive response patterns were generated. Further analysis of drinking ultrastructure revealed that baclofen altered the patterns of these repetitive responses by lengthening the self-initiated intertrial intervals. CONCLUSIONS: Systemic baclofen administration attenuates responding for alcohol and sucrose reinforcement in a dose-dependent manner. If the reinforcing efficacy and response requirement for sucrose and alcohol are matched, then baclofen has similar effects on responding and patterns of drinking microstructure. We conclude that the neural mechanisms that support both ethanol and sucrose self-administration behavior are sensitive to gamma-aminobutyric acid type B modulation.
BACKGROUND:Baclofen, a gamma-aminobutyric acid type B agonist, has been proposed as a pharmacotherapeutic agent in the treatment of addictive disorders such as alcoholism. Preclinical studies documenting the effect of baclofen on alcohol intake have provided conflicting results. The goal of this study was to determine the effect of baclofen pretreatment on ethanol- and sucrose-reinforced responding. METHODS: Animals were trained to self-administer a 10% ethanol in water solution on a fixed ratio 1 schedule of reinforcement by using the sucrose-fade method. With a within-subject design, the effect of three doses of baclofen (1.8, 3.2, and 5.6 mg/kg intraperitoneally) was examined on 10% ethanol- and 2% sucrose-reinforced responding. Dose-dependent effects on responding and on drinking-pattern microstructure were examined. RESULTS: Under a fixed ratio 1 schedule, baclofen reduced responding for alcohol and sucrose reinforcement in a similar, dose-dependent manner. A dose-dependent response attenuation was seen during the initial segment of an operant session when highly repetitive response patterns were generated. Further analysis of drinking ultrastructure revealed that baclofen altered the patterns of these repetitive responses by lengthening the self-initiated intertrial intervals. CONCLUSIONS: Systemic baclofen administration attenuates responding for alcohol and sucrose reinforcement in a dose-dependent manner. If the reinforcing efficacy and response requirement for sucrose and alcohol are matched, then baclofen has similar effects on responding and patterns of drinking microstructure. We conclude that the neural mechanisms that support both ethanol and sucrose self-administration behavior are sensitive to gamma-aminobutyric acid type B modulation.
Authors: Eric Augier; Russell S Dulman; Ruslan Damadzic; Andrew Pilling; J Paul Hamilton; Markus Heilig Journal: Neuropsychopharmacology Date: 2017-03-15 Impact factor: 7.853