The roles of brain noradrenaline and dopamine in the anorectic activity of diethylpropion in rats: a comparison with d-amphetamine.

The anorectic activity of diethylpropion and d-amphetamine was studied in rats subjected to various treatments known to affect brain monoamines. The effect of diethylpropion, like that of d-amphetamine, was completely prevented by a lesion of the ventral noradrenergic bundle, which selectively decreases brain noradrenaline, but was not significantly modified in desipramine pretreated rats by an intraventricular injection of 6-hydroxydopamine, a condition decreasing only dopamine. Pretreatment with penfluridol significantly reduced the effect of d-amphetamine but not that of diethylpropion. A non-significant reduction of drug effect was found with alpha-methyl-p-tyrosine. Lesion of the nucleus medianus raphe, which destroys central serotonin neurons, or treatment with methergoline, a central serotonin antagonist, caused no changes in the effects of both compounds. The findings show that integrity of central noradrenergic neurons is an important condition for diethylpropion and d-amphetamine to exert their anorectic effect. Dopamine does not seem to play any role in the effect of diethylpropion but might contribute to that of d-amphetamine. The data are against any involvement of brain serotonin in diethylpropion anorexia.