ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract:κ-Opioid receptor agonists prevent alterations indopamine neurotransmission that occur in response to repeated cocaineadministration. The present microdialysis study examined whetheradministration of the selective κ-opioid receptor agonist U69593 withmethamphetamine prevents alterations in dopamine levels produced by neurotoxicdoses of methamphetamine. Swiss Webster mice were injected intraperitoneallywith methamphetamine (10.0 mg/kg) or saline, four times in 1 day, at 2-hintervals. Prior to the first and third injection, they received U69593 (0.32mg/kg s.c.) or vehicle. Microdialysis was conducted 3, 7, or 21 days later.Basal and K+-evoked (60 and 100 mM) dopamine overflow werereduced 3 days after methamphetamine administration. These effects werelong-lasting in that they were still apparent 7 and 21 days aftermethamphetamine treatment. Intrastriatal (5.0 and 50 μM) orsystemic (1.0-10.0 mg/kg) administration of methamphetamine increased dopamineconcentrations in control animals. In mice preexposed to methamphetamine,methamphetamine-evoked dopamine overflow was reduced. In animals that hadreceived methamphetamine with U69593, basal dopamine levels did not differfrom those of vehicle-treated controls. U69593 treatment attenuated thedecrease in K+-evoked dopamine produced by prior methamphetamine exposure. The reduction in methamphetamine-evoked dopamine levels was also attenuated. The administration of U69593 alone did not modify basal or stimulus-evoked dopamine levels. These data demonstrate that repeated methamphetamine administration reduces presynaptic dopamine neuronal function in mouse striatum and that co-administration of a selective κ-opioid receptor agonist with methamphetamine attenuates these effects. U69593 treatment did not modify the hyperthermic effects of methamphetamine, indicating that this κ-opioid receptor agonist selectively attenuates methamphetamine-induced alterations in dopamine neurotransmission.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0741553.x
