The antagonizing effect of aspartic acid on morphine withdrawal and levallorphan-precipitated abstinence syndrome signs and on associated changes in brain levels of free amino acids in the rat.

We have previously demonstrated the antagonizing effect of aspartic acid on some effects of morphine and on the development of physical dependence on, and tolerance to, morphine. In the present study, we have withdrawal from morphine or administration of a morphine antagonist. For this purpose sixty five white rats were given morphine and aspartic acid separately and in combination in a 5% saccharose solution instead of drinking water for 30 days. Some of the dependent rats were then withdrawn and others were injected with levallorphan. Flying, jumping, wet-dog shaking, body weight loss and motor activity were estimated and free amino acid levels in the brain were determined. Aspartic acid was found to prevent or antagonize the behavioural signs and the changes in the free amino acid levels in the brain. The results are discussed in the light of the previous data.

Dopaminergic drugs antagonize the psychotomimetic effects of partial-agonist analgesics.

The psychotomimetic actions of the partial-agonist analgesic drugs cyclazocine and levallophan have been demonstrated using a quantitative behavioural test in young rats which measures lateral head movements and pivoting on the hind paws. This drug induced behaviour is antagonized by low doses of the dopaminergic agonists apomorphine and piribedil, the dopamine releasing drug amphetamine, the dopamine reuptake blocking agent benztropine and by large doses of the dopamine precursor L-Dopa. Naloxone antagonize the behaviour, but only at one hundred times the analgesic antagonist dose. These results show that dopaminergic systems are implicated in the mechanism of action of partial-agonist induced psychotomimetic side effects.

Failure of antiserotonergic agents to modify levallorphan-induced stereotypy in rats.

The possibilty that the stereotypic behaviour induced by levallorphan, a narcotic antagonist, might be influenced by a serotonergic system was examined. Two antiserotonergic agents, methysergide and parachlorophenylalanine, failed to modify such stereotypy implying that serotonin is not involved. It is suggested that dopamine might be the principle mediator of this behaviour.