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

Abstract

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

Interaction of CB₁ receptor agonist arachidonylcyclopropylamide with behavioural sensitisation to morphine in mice

“…The first dose of ACPA elicited a significant decrease in locomotor behaviour in the present study which is consistent with the results of a previous experiment using the same dose of this substance for evaluation of its influence on the development of metamphetamine behavioural sensitisation (Landa et al 2014b). However, these findings to some extent run counter to the results of another of our previous studies in which the less selective CB 1 receptor agonist methanandamide (the synthetic analogue of endocannabioid anandamide) did not elicit any changes in mouse locomotion (Landa et al 2006).…”

“…Although the majority of reports speak in favour of cross-sensitisation to opioids after repeated CB 1 receptor agonist administration (Cadoni et al 2001;Lamarque et al 2001;Manzanedo et al 2004) the results presented in this paper suggest inhibition of this phenomenon. In fact, the data obtained in the present study with morphine mirror the results from our previous investigation in which repeated pretreatment with the cannabinoid CB 1 receptor agonist methanandamide elicited cross-sensitisation to the stimulatory drug methamphetamine (Landa et al 2006;Landa et al 2011), whereas the more selective CB 1 receptor agonist ACPA supressed this phenomenon (Landa et al 2014b). …”

The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

“…locomotion) and that these substances have addictive potential (Fattore et al 2008;Landa et al 2014a;Landa et al 2014b). On the other hand, other drug classes with even stronger effects on the CNS and addictive properties have been used therapeutically in both humans and veterinary medicine for centuries (e.g.…”