Neurokinin3 receptor antagonism attenuates cocaine's behavioural activating effects yet potentiates its dopamine-enhancing action in the nucleus accumbens core

TY - JOUR

T1 - Neurokinin3 receptor antagonism attenuates cocaine's behavioural activating effects yet potentiates its dopamine-enhancing action in the nucleus accumbens core

AU - Jocham, G

AU - Lezoch, K

AU - Müller, C.P.

AU - Kart-Teke, E

AU - Huston, J.P.

AU - de Souza Silva, M.A.

PY - 2006/9

Y1 - 2006/9

N2 - Several lines of evidence indicate a role for neurokinin3 receptors (NK3-Rs) in behavioural activation and mechanisms governing reinforcement processes. In this study we investigated the effect of pretreatment with the NK3-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 NK3-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 NK3-Rs in the acute behavioural and neurochemical effects of cocaine, involving dopaminergic activity in the core of the nucleus accumbens.

AB - Several lines of evidence indicate a role for neurokinin3 receptors (NK3-Rs) in behavioural activation and mechanisms governing reinforcement processes. In this study we investigated the effect of pretreatment with the NK3-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 NK3-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 NK3-Rs in the acute behavioural and neurochemical effects of cocaine, involving dopaminergic activity in the core of the nucleus accumbens.

U2 - 10.1111/j.1460-9568.2006.05041.x

DO - 10.1111/j.1460-9568.2006.05041.x

M3 - Article

SN - 1460-9568

VL - 24

SP - 1721

EP - 1732

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

IS - 6

ER -