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Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation.
Neuroscience. 2001; 107(4):629-39.N

Abstract

Rewarding hypothalamic brain stimulation is thought to depend on trans-synaptic activation of high-threshold (and thus rarely directly depolarized by rewarding stimulation) dopaminergic fibers of the medial forebrain bundle. We used in vivo microdialysis and high-performance liquid chromatography coupled with electrochemical or fluorometric detection to investigate the concurrent release of dopamine and glutamate in the nucleus accumbens septi and in the ventral tegmental area, as a function of lateral hypothalamic self-stimulation.Self-stimulation at a variety of stimulation frequencies and pulse widths increased levels of dopamine and its primary metabolites, dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens. Lateral hypothalamic self-stimulation also induced significant increases in ventral tegmental area dopamine and metabolite levels, and the percentage increase of dopamine was higher in this region than in the nucleus accumbens. Local perfusion with the dopamine uptake inhibitor nomifensine (10 microM) increased dopamine levels in the nucleus accumbens about three-fold and potentiated the increase of dopamine levels induced by self-stimulation. Nomifensine perfusion also induced a delayed decrease in nucleus accumbens glutamate levels, and self-stimulation did not modify this effect of the drug. Local perfusion with the D2-type dopamine receptor antagonist raclopride significantly increased both basal and self-stimulation induced dopamine release in the nucleus accumbens. Neither nomifensine nor raclopride perfusion significantly affected the maximal rates of self-stimulation. Perfusion with tetrodotoxin (2 microM) into nucleus accumbens significantly decreased basal and prevented stimulation-induced increases in accumbens dopamine levels but only slightly decreased the rate of self-stimulation. In contrast, perfusion of tetrodotoxin (0.5 microM) into the ventral tegmental area decreased basal and blocked stimulation-induced increases in both nucleus accumbens and ventral tegmental area dopamine levels; this treatment also blocked or strongly inhibited self-stimulation. While it had no effect on glutamate levels in the nucleus accumbens, lateral hypothalamic self-stimulation induced a significant and tetrodotoxin-sensitive increase in glutamate levels in the ventral tegmental area. Taken together, the present results indicate that, across a broad range of stimulation parameters, rewarding lateral hypothalamus stimulation causes major and persistent activation of the mesolimbic dopamine system, and suggest descending glutamatergic fibers in the medial forebrain bundle as a candidate for the directly activated descending pathway in lateral hypothalamus brain stimulation reward.

Authors+Show Affiliations

Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, QC, Canada. zyou@intra.nida.nih.govNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11720786

Citation

You, Z B., et al. "Dopamine and Glutamate Release in the Nucleus Accumbens and Ventral Tegmental Area of Rat Following Lateral Hypothalamic Self-stimulation." Neuroscience, vol. 107, no. 4, 2001, pp. 629-39.
You ZB, Chen YQ, Wise RA. Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation. Neuroscience. 2001;107(4):629-39.
You, Z. B., Chen, Y. Q., & Wise, R. A. (2001). Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation. Neuroscience, 107(4), 629-39.
You ZB, Chen YQ, Wise RA. Dopamine and Glutamate Release in the Nucleus Accumbens and Ventral Tegmental Area of Rat Following Lateral Hypothalamic Self-stimulation. Neuroscience. 2001;107(4):629-39. PubMed PMID: 11720786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine and glutamate release in the nucleus accumbens and ventral tegmental area of rat following lateral hypothalamic self-stimulation. AU - You,Z B, AU - Chen,Y Q, AU - Wise,R A, PY - 2001/11/27/pubmed PY - 2002/3/7/medline PY - 2001/11/27/entrez SP - 629 EP - 39 JF - Neuroscience JO - Neuroscience VL - 107 IS - 4 N2 - Rewarding hypothalamic brain stimulation is thought to depend on trans-synaptic activation of high-threshold (and thus rarely directly depolarized by rewarding stimulation) dopaminergic fibers of the medial forebrain bundle. We used in vivo microdialysis and high-performance liquid chromatography coupled with electrochemical or fluorometric detection to investigate the concurrent release of dopamine and glutamate in the nucleus accumbens septi and in the ventral tegmental area, as a function of lateral hypothalamic self-stimulation.Self-stimulation at a variety of stimulation frequencies and pulse widths increased levels of dopamine and its primary metabolites, dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens. Lateral hypothalamic self-stimulation also induced significant increases in ventral tegmental area dopamine and metabolite levels, and the percentage increase of dopamine was higher in this region than in the nucleus accumbens. Local perfusion with the dopamine uptake inhibitor nomifensine (10 microM) increased dopamine levels in the nucleus accumbens about three-fold and potentiated the increase of dopamine levels induced by self-stimulation. Nomifensine perfusion also induced a delayed decrease in nucleus accumbens glutamate levels, and self-stimulation did not modify this effect of the drug. Local perfusion with the D2-type dopamine receptor antagonist raclopride significantly increased both basal and self-stimulation induced dopamine release in the nucleus accumbens. Neither nomifensine nor raclopride perfusion significantly affected the maximal rates of self-stimulation. Perfusion with tetrodotoxin (2 microM) into nucleus accumbens significantly decreased basal and prevented stimulation-induced increases in accumbens dopamine levels but only slightly decreased the rate of self-stimulation. In contrast, perfusion of tetrodotoxin (0.5 microM) into the ventral tegmental area decreased basal and blocked stimulation-induced increases in both nucleus accumbens and ventral tegmental area dopamine levels; this treatment also blocked or strongly inhibited self-stimulation. While it had no effect on glutamate levels in the nucleus accumbens, lateral hypothalamic self-stimulation induced a significant and tetrodotoxin-sensitive increase in glutamate levels in the ventral tegmental area. Taken together, the present results indicate that, across a broad range of stimulation parameters, rewarding lateral hypothalamus stimulation causes major and persistent activation of the mesolimbic dopamine system, and suggest descending glutamatergic fibers in the medial forebrain bundle as a candidate for the directly activated descending pathway in lateral hypothalamus brain stimulation reward. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/11720786/Dopamine_and_glutamate_release_in_the_nucleus_accumbens_and_ventral_tegmental_area_of_rat_following_lateral_hypothalamic_self_stimulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306452201003797 DB - PRIME DP - Unbound Medicine ER -