Neurokinin receptor antagonism attenuates cocaine's behavioural activating effects yet potentiates its dopamine-enhancing action in the nucleus accumbens core.
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 approximately 350% in the core and approximately 450% in the shell. Pre-treatment with SR142801 significantly potentiated this effect in the core (to approximately 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.
Jocham
Gerhard
G
Institute of Physiological Psychology and Center for Biological and Medical Research, University of Düsseldorf, Universitätsstr.1, D-40225, Düsseldorf, Germany. desouza@uni-duesseldorf.de
Lezoch
Katharina
K
Müller
Christian P
CP
Kart-Teke
Emriye
E
Huston
Joseph P
JP
de Souza Silva
M Angélica
MA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D045604:Extracellular Fluid / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*
D014150:Antipsychotic Agents; D018765:Dopamine Uptake Inhibitors; D010880:Piperidines; D018042:Receptors, Neurokinin-3; D015102:3,4-Dihydroxyphenylacetic Acid; D003042:Cocaine; C091554:SR 142801; D004298:Dopamine; D006719:Homovanillic Acid