Premium
Evidence for D2 receptor mediation of amphetamine‐induced normalization of locomotion and dopamine transporter function in hypoinsulinemic rats
Author(s) -
Sevak Rajkumar J.,
Owens W. Anthony,
Koek Wouter,
Galli Aurelio,
Daws Lynette C.,
France Charles P.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04358.x
Subject(s) - amphetamine , raclopride , dopamine transporter , medicine , endocrinology , dopamine , pharmacology , dopamine receptor d2 , receptor , chemistry , dopaminergic
Dopamine (DA) D2 receptors regulate DA transporter (DAT) activity, and mediate some behavioral effects of amphetamine. DA clearance and amphetamine‐stimulated locomotion are reduced in hypoinsulinemic [streptozotocin (STZ)‐treated] rats, and these deficits are normalized by repeated treatment with amphetamine. Here, a role for D2 receptors in mediating amphetamine‐induced normalization of these parameters was investigated. One week after a saline or STZ injection (50 mg/kg), rats were treated with amphetamine (1.78 mg/kg), raclopride (0.056 mg/kg), saline, or combinations thereof, every‐other‐day for 8 days with locomotor activity measured following each treatment. Conditioned place preference (CPP) for amphetamine and in vivo chronoamperometry to measure DA clearance were carried out on days 17 and 18, respectively, after STZ or saline. Baseline locomotion and DA clearance were significantly reduced in STZ‐treated rats compared with control rats. In STZ‐treated rats, amphetamine treatment normalized DA clearance, and restored the locomotor‐stimulating effects of amphetamine. Raclopride prevented normalization of these parameters. Amphetamine produced CPP in both STZ‐treated and control rats; raclopride significantly attenuated amphetamine‐induced CPP in control and not in STZ‐treated rats. These results support a role for D2 receptors in regulating DA transporter activity, and further demonstrate that D2 receptors contribute to changes in sensitivity to amphetamine in hypoinsulinemic rats.