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Neurokinin 3 receptor antagonism attenuates cocaine's behavioural activating effects yet potentiates its dopamine‐enhancing action in the nucleus accumbens core
Author(s) -
Jocham Gerhard,
Lezoch Katharina,
Müller Christian P.,
KartTeke Emriye,
Huston Joseph P.,
De Souza Silva M. Angélica
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.05041.x
Subject(s) - nucleus accumbens , dopamine , dopaminergic , neurochemical , microdialysis , conditioned place preference , chemistry , pharmacology , antagonism , eticlopride , neuroscience , medicine , psychology , receptor , biology , sch 23390 , biochemistry
Several lines of evidence indicate a role for neurokinin 3 receptors (NK 3 ‐Rs) in behavioural activation and mechanisms governing reinforcement processes. In this study we investigated the effect of pretreatment with the NK 3 ‐R antagonist, SR142801, (0.2 and 2.0 mg/kg) on the cocaine‐induced (10.0 mg/kg i.p.) increase in extracellular dopaminergic activity in the nucleus accumbens (NAc). In vivo microdialysis in the NAc of freely moving rats showed that cocaine increased concentrations of dopamine (DA) to ∼350% in the core and ∼450% in the shell. Pre‐treatment with SR142801 significantly potentiated this effect in the core (to ∼550%), whereas this effect was not found in the shell. We also investigated the effects of NK 3 ‐Rs antagonism on cocaine‐induced hyperactivity and conditioned place preference. SR142801 blocked the hyperactivity, but neither the conditioned place preference nor the conditioned locomotor activity induced by cocaine, although there was a slight tendency towards a reduced place preference. When given alone, SR142801 had no effects on behaviour or extracellular dopamine concentrations in any of the structures investigated. These data provide evidence for a contribution of NK 3 ‐Rs in the acute behavioural and neurochemical effects of cocaine, involving dopaminergic activity in the core of the nucleus accumbens.