Minehiro Moriyama

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.

Effects of antianxiety and antipsychotic drugs on DRL responding for brain stimulation

Satiated rats could be trained to give stable rates of responding for rewarding stimulation of the lateral hypothalamus delivered on differential reinforcement of low rate (DRL) schedule requiring 2 to 8 sec interresponse intervals for reinforcement (DRL-2 to 8). The performance on a DRL-8 schedule was tested 30 min after the oral administration of benzodiazepines. Diazepam (5 and 10 mg/kg) and meprobamate (200 mg/kg) caused significant increases in response rates during the first 5 min of a session, but not thereafter. Bromazepam (1 and 5 mg/kg) also caused a significant increase in the rates during the first and second 5 min. On the other hand, chlorpromazine (20 mg/kg) caused no effect in the first 5 min but decrease in second and third 5 min. These results indicate that DRL schedules with a brain stimulation reward provided a useful tool for evaluation of antianxiety drugs. The advantage of the brain stimulation reward over food reward is that the possible effects of the drugs on hunger motivation need not be considered.

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.