"High impulsivity levels may be a risk factor for nicotine dependence, leading to its initiation and maintenance. Further, numerous studies have shown that ?-aminobutyric acid B (GABAB) receptor antagonists show cognitive enhancing effects. Little is known about the effects of GABAB receptor agonists or positive allosteric modulators (PAMs) in cognitive processes (e.g., attentional performance) and impulsivity/compulsivity. GABAB receptor PAMs may be potentially improved therapeutic compounds for the treatment of disorders, such as drug dependence, or cognitive impairment, than GABAB receptor agonists due to fewer adverse side-effects. In different experiments, BHF177 , a GABAB receptor PAM , decreased both the reinforcing and motivational effects of nicotine without affecting motivation for natural reinforcers, such as food, using the nicotine self-administration fixed-ratio 5 and progressive ratio procedures, respectively, both in rats from the general population as well as in high and low impulsive rats in a similar manner. Interestingly, BHF177 had a larger magnitude of effect in low impulsive rats at the highest dose tested. High/low impulsivity animals were selected based on the poor inhibitory control aspect of impulsivity, as assessed in the 5-choice serial reaction time task (5-CSRTT). Further, BHF177 dose-dependently and selectively blocked cue-induced reinstatement of nicotine seeking, a putative animal model of relapse in humans, and not food seeking, while chronic treatment with BHF177 decreased nicotine self-administration with only small tolerance developed in the general population. Further, BHF177 showed significantly fewer adverse effects than the GABAB receptor agonist CGP44532 in the 5-CSRTT. Thus, BHF177 , or other similar GABAB receptor PAMs, could be useful therapeutics for the treatment of different aspects of nicotine dependence..."