title: Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat.
abstract: Withdrawal from psychostimulants, including methamphetamine, induces a depressive state associated with lethargy, dysphoria, hyperphagia and psychomotor retardation. Previous work with repeated administration of amphetamine in rats has shown that amphetamine withdrawal produces decreased motivation to work for a non-drug reward, and this withdrawal is reversed by administration of a dopamine partial agonist. The purpose of the present study was to examine decreased motivation to work for a non-drug reward during methamphetamine withdrawal and explore the effects of a dopamine agonist, dopamine partial agonist, and indirect monoamine agonist on methamphetamine withdrawal. During withdrawal from repeated methamphetamine administration, rats showed reduced responding for a sweet solution in a progressive-ratio schedule of reinforcement, and this effect was significantly more pronounced than previously observed with amphetamine. Repeated systemic treatment with the dopamine partial agonist terguride (0.2 and 0.4 mg/kg, i.p., twice daily), the full dopamine agonist ropinirole (1 mg/kg, i.p., twice daily), and acetyl-L-carnitine (60 and 100 mg/kg, i.p.), a compound with a potential antidepressant effect, during methamphetamine withdrawal restored responding for the sweet solution, suggesting that these drugs may represent potential therapeutic strategies for the treatment of methamphetamine addiction during the withdrawal phase.
authors.affiliation: Molecular and Integrative Neurosciences Department, SP30-2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hoefer
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Voskanian
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Luigi
authors.initials: L
authors.lastname: Pulvirenti
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003216:Conditioning, Operant; D018491:Dopamine Agonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008090:Lisuride / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009042:Motivation; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology; D013549:Sweetening Agents
chemical_list: D000928:Antidepressive Agents; D018491:Dopamine Agonists; D007211:Indoles; D013549:Sweetening Agents; C046649:ropinirole; C006208:dironyl; D008694:Methamphetamine; D000108:Acetylcarnitine; D008090:Lisuride