A dopaminergic mechanism is involved in the ‘anxiogenic-like’ response induced by chronic amphetamine treatment: a behavioral and neurochemical study

L.M. CANCELA*, A.M. BASSO, I.D. MARTIJENA, N.R. CAPRILES1, V.A. MOLINA

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2001 vol. 909 p. 179 - 186

0006-8993

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 receptors are mainly involved in chronic 1 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 receptors are mainly involved in chronic 1 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 receptors are mainly involved in chronic 11 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. Ó 2001 Published by Elsevier Science B.V. Elsevier Science B.V. Ó 2001 Published by Elsevier Science B.V.