Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: An anatomical, biochemical and pharmacological study

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Abstract

6-Hydroxydopamine (6-OHDA) treatment of neonatal rats resulted in a dose-related loss of striatal dopamine (DA). These reductions correspended closely with the loss of tyrosine hydroxylase-containing terminals at this brain site. Striatal serotonin (5-HT) concentration increased only after DA was maximally depleted by the highest dose of 6-OHDA. Quantitative immunohistochemistry revealed that the increased 5-HT content after neonatal 6-OHDA lesioning was due to a proliferation of 5-HT nerve terminals. The density of immunoreactive 5-HT-containing terminals appeared to increase more than did the 5-HT content. The present study examined whether 5-HT hyperinnervation was playing a role in behavioral responses induced by D1-DA agonists and antagonists in neonatally lesioned rats, because reports have suggested that these drugs may interact with 5-HT receptors. However, SCH-23390, the D1-DA antagonist (0.3 mg/kg), did not alter behavioral responses to 5-HTP and SKF-38393 (3 mg/kg), a D1-DA agonist did not produce any signs of activating 5-HT receptors in 5,7-DHT-lesioned rats. These data indicate that these compounds affecting D1-DA receptors do not have a significant effect on 5-HT function at doses which have maximal effects on D1-DA receptor function. Pretreatment with the 5-HT antagonist methysergide did not produce a change in apomorphine-induced locomotion and did not antagonize the self-mutilation or the other behaviors produced by L-DOPA or SKF-38393 in neonatally lesioned rats, suggesting that 5-HT hyperinnervation is not responsible for these drug-induced changes in neonatal 6-OHDA-lesioned rats.

References (27)

Cited by (104)

  • Effects of prolonged neuronal nitric oxide synthase inhibition on the development and expression of l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats

    2015, Neuropharmacology
    Citation Excerpt :

    The reduction of 5-HT levels might be functional rather than structural and may represent a secondary effect of severe dopaminergic depletion. However, the data regarding striatal 5-HT levels after dopaminergic injury are controversial, and striatal 5-HT levels are reported to remain unchanged (Carta et al., 2007; Dupre et al., 2007; Gil et al., 2011) or increase (Guerra et al., 1997; Rozas et al., 1998; Snyder et al., 1986; Stachowiak et al., 1984; Towle et al., 1989; Zhou et al., 1991). Possible explanations for the discrepancy could be the extent of the lesion, the survival time after lesioning and the site of microinjection.

  • Striatal 6-OHDA lesion in mice: Investigating early neurochemical changes underlying Parkinson's disease

    2010, Behavioural Brain Research
    Citation Excerpt :

    Although the serotonergic and dopaminergic systems are known to critically interact in the pathophysiology of the basal ganglia [22,53], it is not surprising that 5-HT levels are preserved following a moderate DA depletion. Indeed, significant changes in 5-HT levels (namely, compensatory increase or decrease after neonatal and adult 6-OHDA lesion, respectively), were only found after a massive (>90%) DA denervation [31,59,62]. The moderate DA depletion found here, however, was enough to trigger an increase in 5-HT turnover, as revealed by the significant increase in the 5-HIAA/5-HT ratio.

  • The neonate-6-hydroxydopamine-lesioned rat: A model for clinical neuroscience and neurobiological principles

    2005, Brain Research Reviews
    Citation Excerpt :

    Nonetheless, because of ambiguity concerning the means by which specific serotonin receptor subtypes contribute to D1-dopamine receptor sensitization, this area of neonate-lesioned neurobiology should receive additional scrutiny. Accompanying the robust striatal serotonergic hyperinnervation in the neonate-lesioned rats [12,22,107,147,148,157] is an increase in striatal 5-HT receptors, with the greatest elevation observed in 5-HT2 receptor subtypes [131]. In support of altered serotonergic mechanisms in neonate-lesioned rats, m-CPP (meta-chlorophenylpiperazine), a compound presumed to act on 5-HT2C receptors, reportedly enhances chewing, oral activity, head-nodding, and self-biting, after this lesion [3,72,93,95].

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Supported by USPHS Grants HD-03110, MH-36294, NS-21345 and HD-23042.

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