Narcotic agonists and antagonists as models for potential antidepressant drugs

Abstract

The effects of (+)-amphetamine, desmethylimipramine and isocarboxazid on spontaneous locomotor activity and body temperature, together with their activity in two laboratory models of depression produced in mice by the injection of reserpine or tetrabenzine, were compared with those of morphine, cyclazocine and naloxone. Whereas cyclazocine exhibited a weak, transient central stimulant effect, there was no marked similarity between the behavioural effects of morphine or naloxone and those of the representative antidepressants. After peripheral administration, both cyclazocine and morphine antagonised the hypothermia, ptosis and behavioural depression induced by reserpine, but naloxone was inactive. However, following direct injection into the cerebral ventricles, very small doses of all three agents showed anti-reserpine activity. Although morphine, cyclazocine and naloxone could reverse previously established hypothermia and behavioural depression induced by tetrabenaine, pretreatment with these agents could not prevent the depressant effects from developing. The pharmacological behaviour of morphine, cyclazocine and naloxone, together with the known clinical activity of cyclazocine is so far consistent with the possibility that all three may have some component of clinical antidepressant activity.