ISSN:
1432-2072
Keywords:
Key words Methamphetamine
;
Drug discrimination
;
Norepinephrine
;
Desipramine
;
Nisoxetine
;
Isoproterenol
;
Propranolol
;
Methoxamine
;
Prazosin
;
Clonidine
;
Yohimbine
;
Rat
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Rationale:Neurochemical and clinical studies indicate involvement of noradrenergic (NE) neurotransmitter system in the actions of methamphetamine. Objective:The present study investigated NE involvement in the discriminative-stimulus effects of methamphetamine. Methods:In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine, IP, from saline under a fixed-ratio schedule of food presentation, effects of various NE agonists, antagonists and uptake inhibitors were tested. Results: Desipramine (3.0–18.0 mg/kg) and nisoxetine (5.6–30.0 mg/kg), two selective NE-uptake inhibitors, did not significantly generalize to methamphetamine when administered alone, but 5.6 mg/kg desipramine and 10.0 mg/kg nisoxetine significantly shifted the methamphetamine dose-response curve to the left. The beta NE agonist, isoproterenol (0.56–3.0 mg/kg), and antagonist, propranolol (1.0–18.0 mg/kg), neither generalized to methamphetamine when given alone nor altered the discriminative-stimulus effects of methamphetamine when administered in combination. The alpha-1 NE agonist methoxamine (1.0–5.6 mg/kg) failed to generalize to the methamphetamine training stimulus. When given in combination with methamphetamine, the alpha-1 NE antagonist, prazosin (1.0 mg/kg), shifted the methamphetamine dose-response curve somewhat to the right and partially blocked the discriminative-stimulus effects of the 1.0 mg/kg training dose of methamphetamine, but these changes were not significant or dose-related, with further increases in prazosin dose (1.8–10.0 mg/kg) either producing similar or smaller changes. The alpha-2 NE agonist, clonidine, partially generalized to methamphetamine at doses of 0.1–0.18 mg/kg and increased drug-appropriate responding at lower doses of methamphetamine, but it partially blocked the discriminative-stimulus effects of higher 0.56–1.0 mg/kg doses of methamphetamine over the same dose range. The alpha-2 NE antagonist, yohimbine, also partially generalized to methamphetamine and blocked the discriminative-stimulus effects of the 1.0 mg/kg training dose of methamphetamine at doses of 5.6–10.0 mg/kg. A lower 3.0 mg/kg dose of yohimbine increased methamphetamine-appropriate responding when given together with low 0.1–0.3 mg/kg doses of methamphetamine. Conclusions:The present data suggest that the NE system plays a modulatory role in the discriminative-stimulus effects of methamphetamine. These effects appear to be mediated through NE uptake sites and alpha-2 receptors, with limited involvement of alpha-1 receptors and beta receptors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002130050950
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