The effect of felbamate on behavioural sensitization to methamphetamine in mice

Abstract

It has been shown that methamphetamine (Met) similary to other psychostimulants induces a progressive augmentation of behavioural responses after repeated administration, so called behavioural sensitisation. Numerous studies refer to an important role for N-methyl-d-aspartate (NMDA) receptors in the development of behavioural sensitisation. Activating antiepileptic drugs of the newer second generation, such as felbamate (Fel), also invoke psychotropic effects. They may possess attention-enhancing and antidepressant activity, causing anxiety, insomnia, and agitation. Although not all pharmacological effects of felbamate are fully elucidated yet, many of its clinical effects may be related to the inhibition of NMDA currents. Thus, the present study was focused on investigating the influence of felbamate on sensitisation to the effects of methamphetamine on mouse locomotor behaviour in the Open field test. Mice of the albino out-bred strain ICR were randomly allocated into four groups and were administered drugs seven times (from the 7<sup>th</sup> to 13<sup>th</sup> day of the experiment) as follows: (a) n<sub>1, 2</sub>: 2.5 mg/kg/day of Met; (b) n<sub>3</sub>: 240 mg/kg/day of Fel; (c) n<sub>4</sub>: Met + Fel. Locomotion in the Open field test was measured (a) after administration of vehicle on the 1<sup>st</sup> experimental day, (b) after the first dose of drugs given on the 7<sup>th</sup> day, and (c) on the 14<sup>th</sup> day after the “challenge doses” given that way (as follows): n<sub>1</sub>: Met; n<sub>2</sub>: Met + Fel, n<sub>3</sub>: Fel; n<sub>4</sub>: Met. The following significant behavioural changes were observed: (1) stimulatory influence of Met and sensitisation after repeated treatment (n<sub>1</sub>); (2) inhibition of Met sensitisation in the case of a challenge dose combined with Fel (n<sub>2</sub>); (3) augmentation of the sensitising effect of Met when sensitisation was induced by pre-treatment with Met + Fel (n<sub>4</sub>); (4) no behavioural effect of the first dose of Fel, but inhibition of locomotion after repeated administration of the drug (n<sub>3</sub>). The prevention of the development of Met sensitization in the group n<sub>2</sub> in which mice received the Met challenge dose with Fel mirrors the results of a majority of similar studies. Most findings are consistent with inhibitory effects of antagonists of the NMDA receptors on the development of sensitisation to amphetamines; nevertheless, also new findings are reported. In the presented paper, combined pre-treatment with Met + Fel in the group n<sub>4</sub> facilitated the development of sensitisation to Met stimulatory effects.