Short communicationBaclofen attenuates cue-induced reinstatement of alcohol-seeking behavior in Sardinian alcohol-preferring (sP) rats
Introduction
Relapse to alcohol use after periods of abstinence is considered the major problem in the treatment of alcohol dependence (O’Brein, 1997). In order to better understand the neurobiological bases of these phenomena and to possibly identify potential pharmacological remedies, two experimental procedures have been proposed to model alcohol relapses in laboratory animals: alcohol deprivation effect (i.e., the robust, although transient, increase in alcohol consumption after a period of abstinence) and reinstatement of alcohol-seeking behavior (i.e., the resumption of extinguished lever pressing for alcohol induced by alcohol-associated cues or environmental stressors) (Spanagel, 2005).
The GABAB receptor agonist, baclofen, has recently gained interest in the alcohol research field due to a demonstrated suppression of several alcohol-related behaviors, including alcohol drinking, alcohol reinforcing and motivational properties, alcohol-stimulated locomotor activity and alcohol-induced conditioned place preference in rodents (Colombo et al., 2000, Colombo et al., 2003b, Bechtholt and Cunningham, 2005, Maccioni et al., 2005, Walker and Koob, 2007). When tested in human alcoholics, baclofen reduced alcohol consumption and craving for alcohol (Addolorato et al., 2002, Flannery et al., 2004), generalizing – to some extent – the data obtained in rodents.
In experiments on alcohol deprivation effect, acute administration of baclofen resulted in the suppression of this extra-intake of alcohol in Sardinian alcohol-preferring (sP) rats (Colombo et al., 2003a, Colombo et al., 2006). The present study was designed to extend to the reinstatement model the investigation on the “anti-relapse” properties of baclofen in sP rats. To this aim, rats were first trained to lever press for alcohol and then exposed to a within-session reinstatement procedure (Bienkowski et al., 1999, Bienkowski et al., 2000, Maccioni et al., 2007). The baclofen dose (3 mg/kg, i.p.) was chosen on the basis of previous results demonstrating that it was totally devoid of sedative and motor-incoordinating effects while being particularly effective in suppressing different alcohol-related behaviors, including alcohol deprivation effect, in sP rats (Colombo et al., 2003a).
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Materials and methods
The experimental procedure was performed in accordance with the European Communities Council Directive (86/609/EEC) and the subsequent Italian Law on the “Protection of animals used for experimental and other scientific reasons”.
Results
Before the first extinction/reinstatement session, all rats responded stably and preferentially on the “active” lever (166.5 ± 18.6 responses/session during the seven post-surgery sessions, corresponding to an average alcohol self-administration of 0.99 ± 0.11 g/kg/session) over the “inactive” lever (0.9 ± 0.1).
Extinction responding on the “active” lever averaged approximately 70 presses/60 min, without any significant difference between the saline and baclofen condition (Fig. 1). Extinction responding
Discussion
The non-contingent presentation of the alcohol-associated stimulus complex reinstated a previously extinguished lever pressing for alcohol in saline-treated sP rats. These data confirm that presentation of a complex of stimuli associated to alcohol may trigger a robust reinstatement of alcohol-seeking behavior in this rat line (Maccioni et al., 2007).
Treatment with baclofen, administered when responding for alcohol was virtually extinguished, reduced this reinstatement of responding. The mean
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