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Aghajanian GK.
“Psychotogenic Drug Action on Chemically Defined Neurons”.
Psychopharmacol. Bull.. 1979;15(1):53-54.
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Abstract
The neurophysiology of psychotogenic drug action on chemically defined neurons was studied in rats. DMT, psilocin, and bufotenin at low doses had a prefer-ential inhibitory action upon presynaptic 5-HT receptors located upon serotonergic neurons in the raphe nuclei. 5-Methoxytryptamine and 5-methoxy-DMT had a preferential action upon presynaptic 5-HT receptors. Single-cell recording and microiontophoretic studies showed that 5-HT receptors undergo marked adaptive changes in response to chronic drug treatments and denervation. When serotonergic pathways were destroyed, postsynaptic neurons gradually showed a marked increase in sensitivity to 5-HT beyond that accounted for through decreased uptake into presynaptic serotonergic elements. A marked increase in sensitivity of postsynaptic neurons to LSD also occurred. Fluoxetine initially suppressed raphe neuronal firing through increasing 5-HT availability. However, after a number of daily injections, serotonergic neurons recovered their spontaneous activity despite continued injections of fluoxetine. A marked decrease in sensitivity to systemically administered LSD also was found. Noradrenergic neurons of the locus coeruleus and dopaminergic neurons of the substantia nigra were equally inhibited by norepinephrine and dopamine. Noradrenergic neurons were powerfully inhibited by clonidine. Dopaminergic neurons were insensitive to the latter but were inhibited by apomorphine. Piperoxane and trifluoperazine also showed marked differential effects on these 2 types of neurons. In neither case did amphetamine appear to have any direct inhibitory effect. The inhibition of dopaminergic neurons by (+)-amphetamines appears to be mediated primarily through a strionigral neuronal feedback loop. The inhibition of noradrenergic neurons of the locus coerulues seems to occur through the release of catecholamines from adrenergic terminals located upon these cells.
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