Neonatal Co-Lesion by DSP-4 and 5,7-DHT Produces Adulthood Behavioral Sensitization to Dopamine D2 Receptor Agonists

Document Type

Article

Publication Date

1-1-2009

Description

To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (50.0 mg/kg, sc) and 5,7- dihydroxytryptamine (5,7-DHT) (37.5 μg icv, half in each lateral ventricle), respectively, were administered to Wistar rats on the first and third days of postnatal ontogeny, and dopamine (DA) agonist-induced behaviors were assessed in adulthood. At eight weeks, using an HPLC/ED technique, DSP-4 treatment was associated with a reduction in NE content of the corpus striatum (> 60%), hippocampus (95%), and frontal cortex (> 85%), while 5,7-DHT was associated with an 80-90% serotonin reduction in the same brain regions. DA content was unaltered in the striatum and the cortex. In the group lesioned with both DSP-4 and 5,7-DHT, quinpirole-induced (DA D2-agonist-agonist) yawning, 7-hydroxy-DPAT-induced (DA D3 agonist) yawning, and apomorphine-induced (non-selective DA agonist) stereotypies were enhanced. However, SKF 38393-induced (DA D1 agonist) oral activity was reduced in the DSP-4 + 5,7-DHT group. These findings demonstrate that DA D2- and D3-agonist-induced behaviors are enhanced while DA D1-agonist-induced behaviors are suppressed in adult rats in which brain noradrenergic and serotoninergic innervation of the brain has largely been destroyed. This study indicates that noradrenergic and serotoninergic neurons have a great impact on the development of DA receptor reactivity (sensitivity).

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