Central action of narcotic analgesics. I. Catalepsy and stereotypy in rats and narcotic analgesics.

The action of four analgesics, belonging to various pharmacological groups (morphine, codeine, fentanyl, pentazocine), was investigated in rats in tests for catalepsy and stereotypy, the tests depending on dopaminergic brain mechanisms. Interactions of the analgesics with a number of compounds known to affect dopaminergic brain functions in tests of catalepsy and stereotypy were also studied. In some experiments nalorphine, an antagonist of narcotic analgesics, was used. Morphine, codeine and fentanyl produced catalepsy, while pentazocine, at doses up to 60 microgram/kg, did not produce this effect. Reserpine, 2 mg/kg 3 hr before drugs, potentiated catalepsy produced by analgesics, while haloperidol, 0.2 mg/kg, 2 hr earlier, did not influence morphine and codeine catalepsy, but moderately potentiated fentanyl-induced catalepsy. alpha-methyl-p-tyrosine potentiated the cataleptogenic action of fentanyl and codeine, and also, less markedly, the action morphine. D-amphetamine (2.5-10 mg/kg) and apomorphine (5 mg/kg) moderately antagonized the catalepsy induced by analgesics, while atropine did not affect it. Nalorphine, 5 mg/kg, effectively abolished the catalepsy produced by narcotic analgesics, but did not affect that produced by neuroleptics. Morphine, codeine and fentanyl slightly inhibited apomorphine stereotypy, and evidently antagonized stereotypy produced by amphetamine. Pentazocine did not affect or slightly potentiated the both types of stereotypy. It is concluded that morphine, codeine and fentanyl, in contrast to pentazocine, inhibit behavioral activities depending on central dopaminergic functions in the rat. The mechanism of this action is most probably indirect, and seems to be related to the dopaminergic presynaptic functions.