The effects of lamotrigine on alcohol seeking and relapse.
Lamotrigine is a clinically used drug, which inhibits Na(+) channel activity that in turn reduces glutamate release. Its downstream activity on other neurotransmitter systems such as serotonergic and dopaminergic has also been reported. Since both glutamate and monoamines might be involved in alcohol craving and relapse, our aim was to examine the effects of lamotrigine on alcohol seeking and relapse-like drinking behaviour. Thus, lamotrigine (5 and 15mg/kg) was tested in two behavioural models for alcohol seeking and relapse - the model of cue-induced reinstatement of alcohol-seeking behaviour and the alcohol deprivation effect (ADE) model in long-term alcohol drinking Wistar rats. Administration of 5mg/kg of lamotrigine caused a significant decrease of cue-induced reinstatement of alcohol-seeking behaviour. The ADE was significantly reduced with both doses tested. However, the highest dose of lamotrigine produced sedation. The ability of lamotrigine to reduce alcohol seeking as well as relapse-like drinking behaviour provides further support for the proposed involvement of the glutamatergic and dopaminergic/serotonergic systems in alcohol craving and relapse, hence suggesting a good rationale for pharmacological intervention that may reduce craving and relapse in alcohol dependent patients.
Vengeliene
Valentina
V
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, 68159 Mannheim, Germany. valentina.vengeliene@zi-mannheim.de
Heidbreder
Christian A
CA
Spanagel
Rainer
R
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage; D000077213:Lamotrigine; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D055502:Secondary Prevention; D012646:Self Administration; D014227:Triazines / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D014227:Triazines; D000431:Ethanol; D000077213:Lamotrigine