In vitro reinforcement of hippocampal bursting by the cannabinoid receptor agonist (-)-CP-55,940

Involvement of cannabinoid receptors in behavioral reinforcement is suggested by widespread human use of marihuana, although animal tests of cannabinoid reinforcement have produced mixed results. Cannabinoid receptors are found in high density in rat hippocampus and other brain areas. Using the hippocampal-slice preparation, we attempted to demonstrate in vitro reinforcement of CA1 bursting with local micropressure applications of the high-affinity synthetic cannabinoid receptor agonist (-)-CP-55,940. Approximately 60% of the tested neurons showed increased burst activity after a series of brief, burst-contingent applications of (-)-CP-55,940 at pipette concentrations of 5 and 10 microM. Identical microinjections of (-)-CP-55,940 administered independently of cellular activity did not increase and usually suppressed hippocampal bursting. Since general stimulation of CA1 activity by (-)-CP-55,940 can thus be ruled out, we conclude that burst-contingent applications of a cannabinoid receptor agonist can reinforce hippocampal firing in vitro.