Behaviour in rats maintained by low differential reinforcement rate: effects of delta 1-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in combination.

Rats were trained to respond according to a low rate differential reinforcement (DRL) 72 sec schedule of operant behaviour. The animals were then tested with delta 1-tetrahydrocannabinol (delta 1-THC), cannabinol, and cannabidiol alone and in combination. Tests with single doses of delta 1-THC (dose-range: 0.3-5.6 mg/kg) and cannabinol (dose-range: 1-56 mg/kg) but not cannabidiol (dose-range 3-100 mg/kg), yielded a dose-related biphasic effect on the response rate. Small doses of delta 1-THC and cannabinol increased the rate of responding, large doses of these agents decreased it. Cannabidiol alone only decreased the rate of responding (occurring at large doses). The rate of reinforcement generally was decreased when response rates increased and vice versa. Cannabidiol (10 and 30 kg/kg), together with delta 1-THC (1 and 3 mg/kg), decreased the response output and increased the rate of reinforcement. Similar results were observed with combinations of cannabinol (10 and 30 mg/kg) and cannabidiol (10 and 30 mg/kg). Combinations of delta 1-THC (0.3 and 1 mg/kg) and cannabinol (1 and 3 mg/kg) also reduced the response rate and there were no significant changes in the rate of reinforcement. Hence the actions of delta 1-THC and cannabinol on behaviour in rats maintained by low rate differential reinforcement were similar (approximate difference in potency 1:10), whereas no stimulation of response rate was demonstrated with cannabidiol. Vehicle and day of testing (Tuesday or Friday) variables were found not to affect the results.

Hyperactivity and instrumental learning deficits in methylazoxymethanol-treated rat offspring.

Several changes of spontaneous motor and learned behaviours were obtained in the male offspring of pregnant rats that were treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg). MAM-treated offspring, when tested at adult ages, showed notable increases in motor activity parameters as measured by direct observation or in automated photocell test cages. This hyperactive state was accompanied by clear impairments by MAM offspring in the acquisition of instrumental learning in a radial arm maze and in a circular swim maze. In Skinner boxes, MAM offspring made fewer responses during the Fixed Ratio (FR) 1 schedule but did not differ from the saline offspring in the acquisition of the difficult differential-reinforcement-of-low-rates (DRL) 72 sec task. Neurochemical assays indicated that the MAM rats had elevated noradrenaline and dopamine levels in several brain regions. These findings are discussed with regard to possible alterations of habituation processes in MAM rats.