Yasuyuki Ichimaru

Ameliorating effects of rolipram on experimentally induced impairments of learning and memory in rodents

The effects of rolipram, a cAMP-specific phosphodiesterase (phosphodiesterase 4) inhibitor, on experimentally-induced amnesia were examined using a 3-panel runway paradigm in rats and a passive avoidance task in mice. Scopolamine, cerebral ischemia induced by four-vessel occlusion and electric convulsive shock impaired working memory in the 3-panel runway task. Rolipram at 0.1 mg/kg reduced the increase in errors induced by scopolamine or cerebral ischemia. Rolipram at 0.32 mg/kg also reduced the increase in errors induced by electric convulsive shock. Dibutyryl cAMP also had similar effects in 3-panel runway experiments. In the passive avoidance task, rolipram reversed the impairments of the avoidance response induced by scopolamine, cycloheximide and electric convulsive shock at 10, 10 and 3 mg/kg, respectively. These results indicate that rolipram ameliorates impairments of learning and memory in rats and mice, and suggest that rolipram might ameliorate the impairments of learning and memory by elevating cAMP levels.

Effects of anxiolytic drugs on escape behavior induced by dorsal central gray stimulation in rats

Each animal was chronically implanted with bipolar electrodes in dorsal central gray matter (DCG) and was trained to press a lever to decrease the DCG-stimulation current. Chlordiazepoxide (5-20 mg/kg, PO), diazepam (2-10 mg/kg, PO) and bromazepam (1-5 mg/kg, PO) produced dose-dependent increases in the DCG-stimulation threshold 1-4 h after administration without affecting motor performance. Meprobamate (200 mg/kg, PO) and pentobarbital (10 mg/kg, PO) also slightly increased the stimulation threshold. Their potency was in the order of bromazepam greater than diazepam greater than chlordiazepoxide greater than pentobarbital greater than meprobamate. The increase in the threshold induced by diazepam (10 mg/kg, PO) was inhibited by the GABA antagonists, bicuculline (1 mg/kg, IP) and picrotoxin (0.1 mg/kg, IP). These results suggest that decreased susceptibility to brain stimulation is involved in suppressing effects of anxiolytic drugs on the escape behavior, and also that the antiaversive action of benzodiazepines may be related to a GABAergic mechanism.

Behavioral suppression using intracranial reward and punishment: effects of benzodiazepines.

Rats were chronically implanted with electrodes aimed at the lateral hypothalamus (LH) and the dorsal central gray (DCG) and trained to press a lever that delivered rewarding stimulation of the LH and punishing stimulation of the DCG. In this situation, both diazepam (5-20 mg/kg, PO) and bromazepam (2-10 mg/kg, PO) caused a marked dose-dependent increase of the lever pressing response in the punished period. In addition, the facilitation of lever pressing in unpunished period was also seen in diazepam (5 and 10 mg/kg). These results show that behavioral suppression on lever pressing maintained self-stimulation reward is inducible following DCG stimulation, and that benzodiazepines exhibit an anti-behavioral suppression effect in this situation.