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Kindling, drugs and decision-making : an exploration of the effect of anticonvulsant drugs and provoked seizures on a rat Gambling Task

University of British Columbia

Impulsivity is a major component of mania in bipolar disorder, and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are also observed in some patients with temporal lobe epilepsy (TLE), in which seizures originate in the amygdala and hippocampal formations, and incidence of pathological gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of bipolar disorder. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioural aspect targeted by these drugs. Patients with damage to the basolateral amygdala (BLA) also show deficits in decision-making, and rats with BLA lesions have shown such deficits in a variety of behavioural tasks. Few studies have looked at the effect of BLA stimulation on risky decision-making. This project first aimed at exploring the effect of the three anticonvulsant drugs currently also used as mood stabilisers- carbamazepine, valproate and lamotrigine- on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). We then investigated the effect of kindling of the BLA on this task, with the aim of antagonizing any behavioural effects with the anticonvulsant drugs. Thirty-two rats in total learned the rGT. Sixteen rats were used in the pharmacology study, and 16 were implanted unilaterally with a bipolar electrode into the BLA and stimulated twice daily until kindling had been established i.e. three class five seizures were observed. Carbamazepine appeared to slow processing speed, decreased premature responses and also blocked the pro-impulsive effect of amphetamine. Kindling increased choice of the small, but immediate reward option P1 and also increased premature responses. However, none of the changes observed were permanent and therefore, we could not assess the effect of carbamazepine on blocking the effect of kindling. Further studies looking at chronic administration of anticonvulsants, and the effect of kindling on acquisition of the rGT, would help us understand the neurobiological mechanisms underlying vulnerability to impairments in decision-making under uncertainty associated with TLE and other psychiatric disorders.

Text

2013-08-29

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/44938

Psychology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/