Effect of local infusion of glutamate analogues into the nucleus accumbens of rats: an electrochemical and behavioural study.
In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of local infusion of glutamate analogues on dopamine (DA) release in rat nucleus accumbens. Infusion of a low dose of NMDA or AMPA (1 mM/0.2 microliter), but not L-glutamate or kainate, was followed a few minutes later by a large but short-lived increase in the extracellular concentration of DA. The involvement of spreading depression was indicated since this response could be repeated only after a short refractory period, and the response magnitude did not seem to be dependent on the dose infused. Furthermore, the increase in DA release was accompanied by a marked negative shift in brain field potential and a similar increase in release could be induced by local infusion of K+. The infusion of NMDA, AMPA or kainate was followed by behavioural activation of the animals but not convulsions. The behavioural response induced by NMDA was dose-dependently reduced by haloperidol, which suggests the involvement of a DA-dependent mechanism in this effect. Co-infusion of the DA transport inhibitors, nomifensine or GBR 12909, failed to alter the DA response to NMDA, while this response was completely blocked by co-infusion of tetrodotoxin or pretreatment with reserpine. It is evident from this study that local infusion of NMDA or AMPA may induce spreading depression in rat nucleus accumbens and that this condition is associated with a vast release of DA and behavioural activation.
Svensson
L
L
Department of Pharmacology, University of Göteborg, Sweden.
Zhang
J
J
Johannessen
K
K
Engel
J A
JA
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D004563:Electrochemistry / Q000379:methods; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009627:Nomifensine / Q000008:administration & dosage / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D005971:Glutamates; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; D009627:Nomifensine; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D012110:Reserpine; C043425:vanoxerine; D007608:Kainic Acid; D004298:Dopamine