NMDA antagonists block restraint-induced increase in extracellular DOPAC in rat nucleus accumbens.
The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists CPP, TCP, PK 26124 and ifenprodil, and of the minor tranquillizer diazepam on stress-induced changes of dopamine metabolism in the nucleus accumbens were investigated in the rat. Dopamine metabolism was assessed by measuring the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) by means of in vivo differential pulse voltammetry with electrochemically pretreated carbon fiber electrodes. Physical immobilization of the rats for 4 min caused a marked and long-lasting increase in extracellular DOPAC levels in the nucleus accumbens. A similar, though shorter-lasting, augmentation of extracellular DOPAC was observed in the nucleus accumbens after systemic administration of the anxiogenic agent methyl-beta-carboline-3-carboxylate (beta-CCM) (10 mg/kg s.c.). Pretreatment with CPP (1 mg/kg i.p.), TCP (3 mg/kg i.p.), PK 26124 (3 mg/kg i.p.), ifenprodil (3 mg/kg i.p.) or diazepam (2 mg/kg i.p.) totally antagonized the immobilization-induced increase in extracellular DOPAC in the nucleus accumbens. Diazepam and the benzodiazepine (omega 1-2) receptor antagonist flumazenil (30 mg/kg i.p.), but not ifenprodil, also antagonized the beta-CCM-induced activation of dopamine metabolism in the nucleus accumbens. Finally, systemic administration of haloperidol (25 micrograms/kg i.p.) increased the extracellular concentrations of DOPAC in the nucleus accumbens, but pretreatment with ifenprodil (3 mg/kg i.p.) did not modify this response. These data indicate that NMDA receptor antagonists prevent the activation of dopamine metabolism in the nucleus accumbens caused by immobilization stress but not by beta-CCM-induced anxiogenic stimulation. These results suggest that NMDA receptor antagonists may possess an anxiolytic-like action in the rodent, which is exerted via neuroanatomical circuits distinct from those acted upon by diazepam.
Serrano
A
A
Laboratoires d'Etudes et de Recherches Synthélabo, Biochemical Pharmacology Group, Bagneux, France.
D'Angio
M
M
Scatton
B
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010648:Phenylacetates / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D019782:Riluzole; D012686:Septal Nuclei / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002243:Carbolines; D003292:Convulsants; D010648:Phenylacetates; D010879:Piperazines; D010880:Piperidines; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D001224:Aspartic Acid; D016202:N-Methylaspartate; D019782:Riluzole; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C036150:beta-carboline-3-carboxylic acid methyl ester; D003975:Diazepam; C010739:ifenprodil