It has been suggested that cannabinoid agonists increase dopamine (DA) transmission in the mesolimbic dopamine system. However, evidence for such an effect is inconsistent. Prepulse inhibition (PPI) of the acoustic startle reflex is a behavioural paradigm that is modulated by an increase of mesolimbic dopamine. This study sought to ascertain whether or not a cannabinoid agonist, CP 55,940, mimicked the effects of amphetamine (a drug which increases dopamine release) on PPI. The first experiment measured the PPI of 16 male Wistar rats injected (i.p.) with different doses of CP 55,940 in a Latin-square design. A second experiment replicated the effects of the first experiment in a between-subjects design, and also examined the effects of using a 5% alcohol solution as a solvent for cannabinoid agonists, in comparison to the more inert detergent, Tween 80. In both experiments, CP 55,940 in Tween 80 significantly reduced basal activity, increased startle onset latencies and increased PPI, effects opposite to those of amphetamine. These results suggest that the net behavioural effects of cannabinoids are opposite to those of amphetamine. In addition, it was found that 1 ml/kg of a 5% alcohol solution has significant behavioural effects on its own, and reverses the effects of CP 55,940 on PPI. (C) 2002 Lippincott Williams Wilkins.