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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 7th to 13th 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 1st experimental day, (b) after the 1st dose of drugs given on the 7th day, and (c) on the 14th day after "challenge doses" given in the following way: n1: saline at the dose of 10 ml/kg, n2, 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 CB1 receptor agonist ACPA, i.e. suppression of cross-sensitisation to morphine. [ABSTRACT FROM AUTHOR]

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 CB1, CB2 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 CB1 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 7th to 13th day of the experiment) were administered drugs as follows:(a) n1 : vehicle at the dose of 10 ml/kg/day; (b) n2 : Met at the dose of 2.5 mg/kg/day; (c) n31 : 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 1st experimental day, (b) after the 1st dose of drugs given on the 7th day, and (c) on the 14th day after the "challenge doses" administered in the following manner: n1 : saline at a dose of 10 ml/kg, n2,3 : 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. [ABSTRACT FROM AUTHOR]