Effects of a psychostimulant drug sydnocarb on rat brain dopaminergic transmission in vivo.
Transcerebral microdialysis was used to evaluate the effect of a psychostimulant drug, sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine), on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dorsal striatum and nucleus accumbens of freely moving rats. Sydnocarb dose dependently (4.4, 8.75 and 17.5 mg/kg, i.p.) induced a relatively modest (up to 350% of control) and long-lasting (up to 6 h) increase in dopamine extracellular level in the rat dorsal striatum. The drug at 8.75 mg/kg, i.p., produced an approximately similar increase in dopamine efflux in the dorsal striatum and in the nucleus accumbens of freely moving rats. Sydnocarb had no effect on DOPAC or HVA extracellular levels in the rat basal ganglia in vivo at any dose studied. It is important that the drug increased the efflux of dopamine in a tetrodotoxin-sensitive and Ca2+-dependent manner. Measurements of behavioral parameters in non-operated rats revealed that sydnocarb markedly increased locomotor activity and induced stereotyped behavior. These data suggest that the stimulant action of sydnocarb is accompanied by a facilitation of central dopaminergic transmission involving an increase in Ca2+-dependent vesicular dopamine efflux.
Gainetdinov
R R
RR
Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow. raul_gainetdinov@cellbio.duke.edu
Sotnikova
T D
TD
Grekhova
T V
TV
Rayevsky
K S
KS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013558:Sydnones / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D000928:Antidepressive Agents; D000697:Central Nervous System Stimulants; D013558:Sydnones; D015102:3,4-Dihydroxyphenylacetic Acid; D013779:Tetrodotoxin; D002118:Calcium; C009257:sidnocarb; D004298:Dopamine; D006719:Homovanillic Acid