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The AT 1 angiotensin II receptor blockade attenuates the development of amphetamine‐induced behavioral sensitization in a two‐injection protocol
Author(s) -
Paz Maria Constanza,
Assis Maria Amparo,
Cabrera Ricardo J.,
Cancela Liliana M.,
Bregonzio Claudia
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20868
Subject(s) - nucleus accumbens , neurochemical , amphetamine , dopaminergic , chemistry , dopamine , sensitization , pharmacology , endocrinology , medicine , neuroscience , psychology
Abstract It has been shown that a single exposure to amphetamine is sufficient to induce long‐term behavioral, neurochemical, and neuroendocrine sensitization in rats. Dopaminergic neurotransmission in the nucleus accumbens and the caudate‐putamen plays a critical role in the addictive properties of drugs of abuse. Angiotensin (Ang) II receptors are found on the soma and terminals of mesolimbic dopaminergic neurons and it has been shown that Ang II acting through its AT 1 receptors facilitates dopamine release. The hypothesis was tested that Ang II AT 1 receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine and that such changes are related to the development of behavioral and neurochemical sensitization. For this purpose, the study examined the expression of amphetamine‐enhanced (0.5 mg kg −1 i.p.) locomotor activity in animals pretreated with candesartan, an AT 1 blocker, (3 mg kg −1 p.o × 5 days), 3 weeks after an amphetamine injection (5 mg kg −1 i.p.). Dopaminergic hyperreactivity was tested by measuring the 3H‐DA release in vitro from caudate‐putamen and nucleus accumbens slices, induced by K + stimulus. It was confirmed the behavioral sensitization in the two‐injection protocol and candesartan pretreatment attenuate this response. It was also found that AT 1 blockade pretreatment did not affect the locomotor response to dopamine agonists. In respect to the neurochemical sensitization tested using ex vivo 3H‐DA release experiments it was found that AT 1 receptor pretreatment blunted the enhanced response induced by K + stimulus. The results support the idea that the development of neuroadaptive changes induced by amphetamine involves brain AT 1 Ang II receptor activation. Synapse, 2011. © 2010 Wiley‐Liss, Inc.