Dopamine, serotonin and tachykinin in self-injurious behavior.
The neurobiologic basis of self-injurious behavior (SIB) in Lesch-Nyhan syndrome and in other neuropsychiatric conditions remains unclear. The purpose of this review is to summarize recent data concerning SIB induced by the dopamine (DA) uptake inhibitor, GBR-12909 (GBR) and to compare the neurochemical data that have accumulated over the years on SIB in neonatal 6-hydroxydopamine (6OHDA) lesioned rats. The DA uptake inhibitor, GBR, upon repeated administration to adult rats elicits SIB that is temporally associated with a reduction of striatal DA (approximately 30%), increased turnover of serotonin and a robust induction of tachykinin transcription resulting in enhanced biosynthesis and presumably release of tachykinins (substance P and neurokinin A). GBR-induced SIB could be blocked by dopaminergic lesions or by D1 or D2 antagonists. Neonatal dopaminergic lesions result in a high degree of DA loss (> 90%) and elevated levels of serotonin. In this model, SIB is precipitated by DA agonists via activation of D1 DA receptors which are in turn linked to an induction of tachykinin biosynthesis and release. The data taken together suggest that (a) a substantial reduction of DA accompanied by an increase in serotonin turnover may be essential conditions that are conducive to the occurrence of SIB, and (b) this phase is either superimposed with, or followed by a D1 and/or D2 DA receptor-linked activation of striatonigral tachykinin neurons resulting in enhanced tachykinin biosynthesis and release that may sustain the SIB. Thus, a dynamic interplay between DA, serotonin and tachykinin neuronal systems of the basal ganglia appear to influence the genesis and/or expression of SIB.
Sivam
S P
SP
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Gary 46408, USA.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000523:psychology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D016728:Self-Injurious Behavior / Q000139:chemically induced / Q000209:etiology*; D012701:Serotonin / Q000502:physiology*; D015320:Tachykinins / Q000502:physiology*
D010879:Piperazines; D015320:Tachykinins; D012701:Serotonin; C043425:vanoxerine; D003042:Cocaine; D004298:Dopamine