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

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<sub>1</sub>, CB<sub>2</sub> 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<sub>1</sub> 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<sup>th</sup> to 13<sup>th</sup> day of the experiment) were administered drugs as follows:(a) n<sub>1</sub>: vehicle at the dose of 10 ml/kg/day; (b) n<sub>2</sub>: Met at the dose of 2.5 mg/kg/day; (c) n<sub> 3</sub>: 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<sup>st</sup> experimental day, (b) after the 1<sup>st</sup> dose of drugs given on the 7<sup>th</sup> day, and (c) on the 14<sup>th</sup> day after the “challenge doses” administered in the following manner: n<sub>1</sub>: saline at a dose of 10 ml/kg, n<sub>2, 3</sub>: 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.