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

Abstract

Activities of the endocannabinoid system are believed to be substantially involved in psychostimulant and opioid addiction. Nevertheless, interactions between cannabinoid and opioid systems are not yet fully understood. Thus, the aim of the present study was to investigate the interaction between morphine and the cannabinoid CB₁ receptor agonist arachidonylcyclopropylamide (ACPA) in behavioural sensitisation. Sensitisation occurs after repeated exposure to drugs of abuse including morphine and cannabinomimetics and it has been suggested to mediate craving and relapses. Male mice were randomly allocated into three groups and were seven times (from the 7^th to 13^th day of the experiment) administered drugs as follows: (a) n₁: vehicle at the dose of 10 ml/kg/day; (b) n₂: morphine at the dose of 10.0 mg/kg/day; (c) n₃: ACPA at the dose of 1.0 mg/kg/day. Changes in locomotor behaviour were measured in the Open Field Test: (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 “challenge doses” given in the following way: n₁: saline at the dose of 10 ml/kg, n_{2, 3}: morphine at the dose of 10.0 mg/kg. Registered behavioural changes unambiguously showed the development of behavioural sensitisation to the stimulatory effects of morphine on locomotion after its repeated administration (P < 0.05). However, surprisingly, taking into account reports on synergistic effects of opioids and cannabinoid receptor stimulation, a significant decrease (P < 0.05) in behavioural sensitisation to morphine occurred when the drug challenge dose was given following repeated pre-treatment with the CB₁receptor agonist ACPA, i.e. suppression of cross-sensitisation to morphine.