Neonatal destruction of rat nigrostriatal dopaminergic fibers results in an enhanced oral activity response to both dopamine (DA) D1 and serotonin (5-HT) agonists. Because cholinergic systems represent another one of the neural circuits involved in oral behavior, it was of interest to determine whether muscarinic receptors might also be sensitized in the lesioned rats. At 3 days after birth, rats were pretreated with desipramine HCl (20 mg/kg, IP) 1 h before 6-hydroxydopamine (6-OHDA) HBr (100 μg in each lateral ventricle) or saline-ascorbic acid (0.1%) vehicle. Between 2 and 4 months, behavioral supersensitivity to a D1 agonist (SKandF 38393) and 5-HT agonist (m-chlorophenylpiperazine; m-CPP) was established before rats were challenged with the muscarinic receptor agonist, pilocarpine HCl (0.125 to 10.0 mg/kg, IP). The pilocarpine dose-effect curve was shifted to the left, with a maximal effect of 63.7 ± 8.6 oral movements being produced by a 1.0 mg/kg pilocarpine HCl dose in the 6-OHDA lesioned rats, versus 15.0 ± 2.4 oral movements in the control group (p < 0.001). The enhanced response to pilocarpine was attenuated by the muscarinic receptor antagonist, scopolamine HCl (0.1 mg/kg IP). These findings indicate that neonatal 6-OHDA treatment produces supersensitization of muscarinic receptors in rats.
Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-13828 |
Date | 01 January 1993 |
Creators | Kostrzewa, Richard M., Neely, David |
Publisher | Digital Commons @ East Tennessee State University |
Source Sets | East Tennessee State University |
Detected Language | English |
Type | text |
Source | ETSU Faculty Works |
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