The effect of felbamate on behavioural sensitization to methamphetamine in mice

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) n 3 :Met + Srt at the doses of 2.5 mg/kg/day + 10.0 mg/kg/day; (c) n 4 : 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: n 1 : Met; n 2 : Met+Srt, n 3 : Met; n 4 : Srt. We found the following significant behavioural changes: (1) a stimulatory influence of Met and development of sensitisation after repeated treatment (n 1 ); (2) an inhibition of Met sensitisation in the case of a combined challenge dose of Met + Srt (n 2 ); (3) a stimulatory effect of Met when animals were repeatedly pre-treated with Met + Srt (n 3 ); (4) a significant inhibition of locomotion after the 1 st dose of Srt, that persisted even after the last Srt dose (n 4 ). 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.Keywords: behavioural sensitisation; methamphetamine; sertindole; mice List of abbreviations AM 251 = N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide,JWH 015 = 1 propyl-2-methyl-3-(1-naphthoyl)indole, Met = methamphetamine, NMDA = N-methyl-d-aspartate, Srt = sertindole, V = vehicle

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The effect of the cannabinoid CB1 receptor agonist arachidonylcyclopropylamide (ACPA) on behavioural sensitisation to methamphetamine in mice

Landa¹,

Šlais²,

Máchalová³

et al. 2014

Vet. Med. - Czech

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ABSTRACT:The psychostimulant methamphetamine (Met), similarly to other drugs of abuse, is known to produce an increased behavioural response after its repeated application (behavioural sensitisation). It has also been described that an increased response to a drug may be elicited by previous repeated administration of another drug (cross-sensitisation). We have previously shown that the CB 1 , CB 2 and TRPV (vanilloid) cannabinoid receptor agonist methanandamide, cross-sensitised to Met stimulatory effects in mice. The present study was focused on ability of the more selective and potent CB 1 receptor activator arachidonylcyclopropylamide (ACPA) to elicit cross-sensitisation to the stimulatory effects of Met on mouse locomotor behaviour in the Open field test. Male mice were randomly divided into three groups and on seven occasions (from the 7 th to 13 th day of the experiment) were administered drugs as follows:(a) n 1 : vehicle at the dose of 10 ml/kg/day; (b) n 2 : Met at the dose of 2.5 mg/kg/day; (c) n 3 : ACPA at the dose of 1.0 mg/kg/day. Locomotor behaviour in the Open field test was measured (a) after administration of vehicle on the 1 st experimental 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 manner: n 1 : saline at a dose of 10 ml/kg, n 2, 3 : Met at a dose of 2.5 mg/kg. The observed behavioural changes consisted in: (a) gradual development of habituation to the open field conditions in three consecutive tests; (b) development of behavioural sensitisation to the stimulatory effects of Met after repeated treatment; (c) insignificant effect of repeated pre-treatment with ACPA on the stimulatory effects of Met challenge dose. The results of our study give rise to the question which of the cannabinoid receptor mechanisms might be most responsible for the neuroplastic changes inducing sensitisation to the stimulatory effects of Met. Keywords

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The effect of felbamate on behavioural sensitization to methamphetamine in mice

Cited by 3 publications

References 37 publications

Implication of NMDA receptors in behavioural sensitization to psychostimulants: A short review

Implication of NMDA receptors in behavioural sensitization to psychostimulants: A short review

The effect of sertindole on behavioural sensitisation to methamphetamine in mice

The effect of the cannabinoid CB1 receptor agonist arachidonylcyclopropylamide (ACPA) on behavioural sensitisation to methamphetamine in mice

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