IN-VITRO REINFORCEMENT OF HIPPOCAMPAL BURSTING BY THE CANNABINOID RECEPTOR AGONIST (-)-CP-55,940

Involvement of cannabinoid receptors in behavioral reinforcement is su ggested by widespread human use of marihuana, although animal tests of cannabinoid reinforcement have produced mixed results. Cannabinoid re ceptors are found in high density in rat hippocampus and other brain a reas. Using the hippocampal-slice preparation, we attempted to demonst rate in vitro reinforcement of CA1 bursting with local micropressure a pplications of the high-affinity synthetic cannabinoid receptor agonis t (-)-CP-55,940. Approximately 60% of the tested neurons showed increa sed burst activity after a series of brief, burst-contingent applicati ons of (-)-CP-55,940 at pipette concentrations of 5 and 10 muM. Identi cal microinjections of (-)-CP-55,940 administered independently of cel lular activity did not increase and usually suppressed hippocampal bur sting. 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 vitr o.