The effect of sertindole on behavioural sensitisation to methamphetamine in mice

Abstract

Similarly to various other addictive substances, methamphetamine (Met) produces, following repeated application, a strong increase in behavioural responses (particularly locomotor behaviour), a phenomenon termed behavioural sensitisation. In our previous studies we tested the effects of various psychotropic drugs on behavioural sensitisation to Met, particularly the effects of cannabinoid receptor ligands with different intrinsic activities and felbamate and memantine, antagonists of N-methyl-d-aspartate (NMDA) receptors. In the present study we investigated the influence of the antipsychotic drug sertindole (Srt) on sensitisation to the effects of Met on mouse locomotor behaviour in the Open field test. Male mice were randomly divided into 4 groups and were administered drugs seven times (from the 7^th to 13^th day of the experiment) as follows: (a) n_{1, 2}: Met at the doses of 2.5 mg/kg/day; (b) n₃: Met + Srt at the doses of 2.5 mg/kg/day + 10.0 mg/kg/day; (c) n₄: Srt at the dose of 10.0 mg/kg/day. Locomotion in the Open field test was measured (a) after administration of vehicle on the 1^st day, (b) after the 1^st dose of drugs given on the 7^th day, and (c) on the 14^th day after the “challenge doses” administered in the following way: n₁: Met; n₂: Met+Srt, n₃: Met; n₄: Srt. We found the following significant behavioural changes: (1) a stimulatory influence of Met and development of sensitisation after repeated treatment (n₁); (2) an inhibition of Met sensitisation in the case of a combined challenge dose of Met + Srt (n₂); (3) a stimulatory effect of Met when animals were repeatedly pre-treated with Met + Srt (n₃); (4) a significant inhibition of locomotion after the 1^st dose of Srt, that persisted even after the last Srt dose (n₄). Data concerning the involvement of sertindole in reward processes associated with drug addiction are not completely consistent and our results reflect this ambiguity to a certain extent. A combined challenge dose of Met + Srt administered after repeated pre-treatment with Met inhibited the development of behavioural sensitisation; on the other hand a Met challenge dose alone administered after repeated pre-treatment with Met + Srt produced a significant increase in locomotion.