Effects of caffeine and L-PIA on rats with selective damage of the hippocampal system

Rats with electrolytic lesions of either the medial septum or hippocampus or with colchicine-induced lesions of the dentate granule cells produced significantly higher amounts of lever pressing as compared to controls on both V150 sec and VT50 sec reinforcement schedules. Caffeine, at doses of 3.2, 10, and 32 mg/kg, produced a dose-related decrease in operant responding for all lesioned animals while having little effect on the responding of controls. L-PIA (an adenosine analog), at doses of 0.01, 0.05, and 0.10 mg/kg, produced similar but more variable effects in some of the groups tested and did not alter the rate-reducing effects of caffeine (32 mg/kg) when given concurrently (0.05 mg/kg). Caffeine administration also appeared to coincide with a long-term decrease in response rates that continued after cessation of its administration. Explanations are advanced as to caffeine's possible mode of action in this experiment. The postulate that colchicine-induced damage of dentate granule cells might be a viable animal model of some forms of hyperactivity also is advanced. This specific lesioning procedure, by itself, produced animals which displayed significantly higher than normal levels of general activity which were also sensitive to caffeine's rate-decreasing effects.