Pharmacological Effects of <i>p</i>-Chloroamphetamine with Respect to Current Amine Hypotheses of Affective Disorders

Abstract

The effects of p-chloroamphetamine (pCA) on the regional distribution of dopamine, noradrenaline and 5-hydroxytryptamine in rat brain were studied at both 3 and 30 days after a single injection. It was found that pCA has no signifícant effect on the levels of dopamine or noradrenaline at either of the times studied. Conversely pCA had an effect on the levels of 5-hydroxytryptamine but the effect was both time and area dependent. pCA has been shown to be an effective antidepressant. Since the levels of 5-hydroxytryptamine were reduced in all areas studied and there was no effect on the levels of the two catecholamines, the results found in the study do not support an amine hypothesis in which these transmitters are implicated.

Effect of Serotonin Depletion Induced by <i>p</i>-Chloroamphetamine on Changes in Rats’ Activity Levels Produced by Lithium

“…The finding that pCA pretreatment af fected brain 5-HT levels selectively is consis tent with the view that the persistent, long term biochemical effects of this drug are spe cific to the 5-HT neuronal system [5,16,21], In addition to the present replication of a decrease in 5-HT levels, pCA has been dem onstrated to decrease 5-HIAA levels, trypto phan hydroxylase activity, 5-HT uptake and turnover [21]. All these effects have been attributed to a single mechanism: B-9 cell group degeneration [7,17], The finding that 21-day lithium administration did not affect NE or DA brain levels is also consistent with other reports [1,9,23].…”

“…The resultant decrease of 5-HT levels observed after combined pCA-lithium treatments is compatible with the suggested neurotoxic action of pCA. If one takes into account the suggestion that lithium increases 5-HT levels through in creases in precursor uptake, an alternative explanation could be that lithium was incap able of reversing pCA effects on 5-HT trans mission because pCA inhibited tryptophan hydroxylase activity to the point that trypto phan was no longer an effective precursor [5].…”

“…The persistent, long-term biochemical effect of p-chloroamphetamine seems to be a specific depletion of 5-HT from neurones that contain this substance [5,21].…”