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SUMMARY:Nicotine dependence\, reward\, impulsivity and attentional perform
 ance:  Taking a step back into the future - Dr Stella Vlachou - Nursing an
 d Human Sciences\, Dublin City University 
DTSTART:20150629T120000Z
DTEND:20150629T130000Z
UID:TALK59699@talks.cam.ac.uk
CONTACT:Lorraine Coulson
DESCRIPTION:Tobacco  smoking  is  partly  attributed  to  the  addictive  
 properties  of  nicotine  and constitutes a worldwide drug abuse problem w
 ith serious health effects. γ-aminobutyric acid (GABA) is the major inhib
 itory neurotransmitter in the brain and is implicated in the modulation of
  brain reward and cognitive processes. Acute or chronic administration of 
 γ-aminobutyric acid B (GABAB) receptor agonists and/or positive allosteri
 c modulators (PAMs) decreases self-administration of various drugs of abus
 e and inhibits cue-induced reinstatement of drug-seeking behavior. Impulsi
 vity\, a tendency to pursue rewarding stimuli without consideration for po
 tential harmful/negative consequences\, is strongly associated with habitu
 al tobacco smoking. High impulsivity levels may be a risk factor for nicot
 ine dependence\, leading to its initiation and maintenance. Further\, nume
 rous studies have shown that γ-aminobutyric acid B (GABAB) receptor antag
 onists 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 impulsi
 vity/compulsivity. GABAB  receptor PAMs may be potentially improved   ther
 apeutic   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 motiv
 ational effects of nicotine without affecting motivation for natural reinf
 orcers\, 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 im
 pulsive 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\, BH
 F177 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 sel
 f-administration with only small tolerance developed in the general popula
 tion. 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 treatm
 ent of different aspects of nicotine dependence\, by assisting both in smo
 king cessation  by decreasing  the  reinforcing effects  of nicotine\,  as
   well  as  in  preventing relapse to smoking in the general population an
 d/or in both high and low impulsive individuals.
LOCATION:Kenneth Craik Room\, Craik Marshall Building\, Downing Site\, Cam
 bridge
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