title: A dopaminergic mechanism is involved in the 'anxiogenic-like' response induced by chronic amphetamine treatment: a behavioral and neurochemical study.
abstract: The purpose of this study was to examine the influence of chronic d-amphetamine (AMPH) treatment (2 mg/kg i.p., for 9 consecutive days) on behavioral and neurochemical responses to a subsequent exposure - 4 days after the last AMPH injection--to the elevated plus-maze (EPM), as well as to determine the involvement of a dopaminergic mechanism in that influence. Results showed that chronic AMPH treatment induced an 'anxiogenic-like' response when animals were evaluated in the EPM test. Pretreatment with either haloperidol (HAL, 1 mg/kg i.p., 20 min prior to each injection) or SCH-23390 (0.1 mg/kg i.p., 10 min prior to each injection) completely abolished the chronic AMPH-induced 'anxiogenic-like' effect displayed in the EPM test. However, sulpiride pretreatment (60 mg/kg i.p., 10 min prior to each AMPH injection) did not modify such effect. In addition, rats treated with AMPH and subsequently exposed to the EPM, showed a decrease in the maximal GABA-stimulated chloride uptake in cortical microsacs. HAL pretreatment restored the maximal chloride uptake induced by chronic AMPH. Altogether, these results suggest that: (1) previous exposure to chronic AMPH treatment induces an increased emotional response following a conflict situation, (2) dopamine D(1) receptors are mainly involved in chronic AMPH-induced changes in the behavior displayed in EPM test, and (3) an interaction between GABAergic and dopaminergic mechanisms may be implicated in neurochemical and behavioral changes induced by chronic AMPH treatment.
authors.affiliation: Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, Córdoba, Argentina. lcancela@fcq.unc.edu.ar
authors.forename: L M
authors.initials: LM
authors.lastname: Cancela
authors.forename: A M
authors.initials: AM
authors.lastname: Basso
authors.forename: I D
authors.initials: ID
authors.lastname: Martijena
authors.forename: N R
authors.initials: NR
authors.lastname: Capriles
authors.forename: V A
authors.initials: VA
authors.lastname: Molina
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018118:Chloride Channels; D002712:Chlorides; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D000661:Amphetamine; D006220:Haloperidol; D004298:Dopamine