Baclofen has opposite effects on escalation of cocaine self-administration: Increased intake in rats selectively bred for high (HiS) saccharin intake and decreased intake in those selected for low (LoS) saccharin intake
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Saccharin
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Baclofen
Acceptable daily intake
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Recent studies have focused on the neurobiological mechanism of relapse which plays a critical role in motivational aspect of compulsive drug-taking behavior and intense drug craving. In this respect, extinction procedure provides a measure of the development of motivational properties of drug seeking during the abstinence of drugs. Previous studies using a variety of cocaine self-administration procedures have shown that the GABA(B) agonist, baclofen, attenuates drug-seeking and drug-taking behavior. However, little is known about the role of baclofen on cocaine seeking behavior during extinction phase without the priming injection of cocaine. The purpose of present study was, therefore, to investigate the effect of baclofen on cocaine seeking behavior after cessation of continuing daily cocaine self-administration under a fixed ratio1 (FR1) schedule of reinforcement. Male Sprague-Dawley rats were trained to self-administer cocaine (1 mg/kg, i.v.) during daily 2-h sessions. When stable response was established by rats after 3 weeks of cocaine self-administration, cocaine was replaced by saline. On the first day of extinction, rats were administrated with baclofen (1.25 or 2.5 mg/kg, i.p.) or saline (1 ml/kg, i.p.) 30 min before the extinction session. Our results showed that pretreatment with 2.5 mg/kg baclofen, but not 1.25 mg/kg, significantly suppressed enhanced non-reinforced responding during extinction session. These results suggest that baclofen may be a potentially effective against cocaine addiction by preventing relapse in the abstinence of cocaine. Supported by R12-2003-002-03001-0
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Extinction (optical mineralogy)
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Baclofen
Self-administration
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Background: Baclofen, a γ‐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 γ‐aminobutyric acid type B modulation.
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Adult male
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ABSTRACT Treatment with gamma-aminobutiric acid (GABA(B)) receptor agonist, +/-baclofen, has been shown to reduce ethanol intake in selectively bred Sardinian alcohol-preferring rats. The general goal of the present study was to characterize the high ethanol consumption high-alcohol-drinking University of Chile bibulous (UChB) rats with regard to the anti-alcohol effect of GABA(B) receptor stimulation. UChB rats were treated with the more active enantiomer of baclofen [R(+)-baclofen; at a dose of 1.0, 2.0 or 3.0 mg/kg] administered intraperitoneally once daily for four consecutive days or a single dose. When comparing ethanol and saccharin consumption in a free-choice regimen with unlimited access 24 hours/day, the dose of baclofen required to attenuate ethanol consumption significantly was 1.0 mg/kg administered once a day for three consecutive days while the dose that was sufficient to affect saccharin consumption significantly was 2.0 mg/kg, indicating that baclofen was more potent in reducing ethanol intake by UChB rats than reducing saccharin consumption. The reduction of ethanol or saccharin intake can not be attributed to baclofen-induced motor impairment, since baclofen (1.0, 2.0 or 3.0 mg/kg) did not alter spontaneous locomotor activity in UChB rats. Baclofen dose-dependently suppressed the motor activity stimulated by ethanol administration, a phenomenon mediated by activation of the mesolimbic dopamine system. In conclusion, these results showed that the activation of GABA(B) receptor by R(+)-baclofen reduced ethanol and saccharin consumption, as well as ethanol-induced motor stimulation, implicating the GABA(B) receptor in the neural substrates mediating effects that sustain voluntary ethanol in take in UChB rats.
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Baclofen
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Saccharin
Self-administration
Extinction (optical mineralogy)
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Background: Baclofen, a γ-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 γ-aminobutyric acid type B modulation.
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Self-administration
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