Effect of benzodiazepines on the central action of narcotic analgesics

The effects of benzodiazepine (mainly diazepam) on the following central action of narcotic analgesics were tested: antinociceptive action (Randall-Selitto and hot plate tests), hypermotility, inhibition of methylphenidate stereotypy, catalepsy. Diazepam, in doses not affecting the pain threshold markedly potentiated morphine, codeine, etorphine, pentazocine and fentanyl antinociception. Hypermotility produced by morphine and fentanyl was inhibited by pretreatment with chlordiazepoxide, diazepam and clonazepam. Diazepam potentiated the inhibitory effect of opiates on methylphenidate-induced stereotyped gnawing in mice and increased the catalepsy induced by morphine and fentanyl in rats. In all experiments the effects of diazepam were suppressed by the substances which impair GABA-ergic neurotransmission: bicuculline and picrotoxin. Obtained results indicate that benzodiazepine potentiate the antinociceptive and cataleptogenic effects of opiates and their inhibitory influence on methylphenidate stereotypy. However, these drugs antagonize locomotor hyperactivity in mice. All these actions seem to be related to facilitation of GABA-ergic neurotransmission by benzodiazepines.