Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release.
The effects of microinfusion of serotonin (5-HT) agents as well as glutamate and muscimol into the ventral tegmental area (VTA) on dopamine (DA) release in the ipsilateral nucleus accumbens (ACC) were investigated in freely moving rats, using a push-pull perfusion procedure. The baseline values for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were approximately 0.24, 8.4, 2.1 and 2.7 pmol/15 min, respectively, in the push-pull perfusate of the ACC. When microinfused into the VTA, glutamate (0.74 microgram) significantly (p less than 0.05) increased the contents of DOPAC (110%) and HVA (90%) over baseline levels in the perfusate. On the other hand, 0.5 microgram muscimol (a gamma-amino-n-butyric acid, GABA, agonist) significantly, (p less than 0.05) decreased both DA (40%) and DOPAC (20%) levels relative to baseline values. Administration of 2 micrograms 5-HT into the VTA caused a significant (p less than 0.05) elevation in the perfusate levels of DOPAC (80%) and HVA (70%) over baseline values. A similar effect was obtained with a nonselective 5-HT1 agonist but not with a selective 5-HT1A agonist. The results suggest that 5-HT innervations in the VTA may have an excitatory action possibly via 5-HT1B rather than 5-HT1A receptors on the mesolimbic DA system projecting to the ACC and that this DA system may also be regulated by glutamatergic and GABAergic (via GABAA receptors) inputs.
Guan
X M
XM
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202-4887.
McBride
W J
WJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000378:metabolism
D005971:Glutamates; D015102:3,4-Dihydroxyphenylacetic Acid; D009118:Muscimol; D012701:Serotonin; D018698:Glutamic Acid; D004298:Dopamine