Central serotonergic mechanisms and development of morphine dependence.

The effects of different manipulations of brain serotonin (5-HT) content on the development of morphine dependence were investigated in rats, which were implanted with morphine pellets for 40 days. Serotonin content was decreased by (a) short or long term inhibition of tryptophan hydroxylase with para-chlorophenylalanine (PCPA), (b) by short or long term degeneration of 5-HT containing nerve terminals with 5,6-dihydroxytryptamine or (c) by degeneration of 5-HT containing nerve terminals by lesioning of midbrain raphe nuclei. With all methods used, the frequency of withdrawal jumping was significantly reduced, while other withdrawal signs remained more or less unchanged. Additional administration of 5-HTP to chronically PCPA treated rats did not reverse the PCPA effect. Since chronic reduction of 5-HT level during the whole time of morphine exposure changed withdrawal symptomatology in nearly the same way as did a decrease in 5-HT level during the time of withdrawal only, it is suggested that serotonergic mechanisms are not linked to the basic processes underlying dependence development but that they are only involved in the nervous pathways mediating the expression of some withdrawal signs.