Differential effects of caffeine, picrotoxin, and pentylenetetrazol on hippocampal afterdischarge activity and wet dog shakes

Abstract

We identified changes in hippocampal afterdischarge activity that follow administration of subconvulsant doses (one-half the convulsant dose) of analeptic agents with known pharmacological action. Long-Evans rats ( N = 104) with chronic bipolar electrodes implanted in the dorsal hippocampus, were injected i.p. with saline, caffeine (75 mg/kg), picrotoxin (2 mg/kg), or pentylenetetrazol (20 mg/kg) in 1 ml/kg volume 15 min before testing. Body temperature was measured at the beginning of the session to determine if significant change was associated with any of the treatments. Beginning at 10 μA, current (2-s train of 50-Hz biphasic pulses) was applied to hippocampal electrodes and intensity was increased in 10-μA steps until the afterdischarge sequence was elicited. Afterdischarge threshold, wet dog shake frequency, and the duration of the primary afterdischarge, the postprimary depression, and the rebound afterdischarge were measured. Caffeine administration produced a dramatic prolongation of the rebound afterdischarge, without affecting the duration of the primary afterdischarge. All other afterdischarge variables were unchanged by the caffeine treatment. Because caffeine blocks adenosine receptors at physiologic concentrations, adenosine action is implicated in the termination of the second, but not the first, spike train. Picrotoxin and pentylenetetrazol had no influence on the EEG, despite evidence of slight (1°C) hypothermia. A decrease in wet dog shake frequency, however, was associated with picrotoxin administration. As picrotoxin and pentylenetetrazol are known γ-aminobutyric acid (GABA) antagonists, the results suggest that GABA is involved minimally, if at all, in the hippocampal afterdischarge sequence.