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Reversal of dopamine inhibition of dopaminergic neurons of the ventral tegmental area is mediated by protein kinase C.
Neuropsychopharmacology 2012; 37(2):543-56N

Abstract

Adaptation of putative dopaminergic (pDA) neurons in the ventral tegmental area (VTA) to drugs of abuse may alter information processing related to reward and reinforcement and is an important factor in the development of addiction. We have demonstrated that prolonged increases in the concentration of dopamine (DA) result in a time-dependent decrease in sensitivity of pDA neurons to DA, which we termed DA inhibition reversal (DIR). In this study, we used extracellular recordings to examine factors mediating DIR. A 40 min administration of DA (2.5-10 μM), but not the DA D2 receptor agonist quinpirole (50-200 nM), resulted in inhibition of neuronal firing followed by DIR. In the presence of 100 nM cocaine, inhibition followed by DIR was seen with much lower DA concentrations. Reversal of quinpirole inhibition could be induced by an activator of protein kinase C, but not of protein kinase A. Inhibitors of protein kinase C or phospholipase C blocked the development of DIR. Disruption of intracellular calcium release also prevented DIR. Reduction of extracellular calcium or inhibition of store-operated calcium entry blocked DIR, but the L-type calcium channel blocker nifedipine did not. DIR was age-dependent and not seen in pDA VTA neurons from rat pups younger than 15 days postnatally. Our data indicate that DIR is mediated by protein kinase C, and implicate a conventional protein kinase C. This characterization of DIR gives insight into the regulation of autoinhibition of pDA VTA neurons, and the resulting long-term alteration in information processing related to reward and reinforcement.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21976045

Citation

Nimitvilai, Sudarat, et al. "Reversal of Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area Is Mediated By Protein Kinase C." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 37, no. 2, 2012, pp. 543-56.
Nimitvilai S, Arora DS, Brodie MS. Reversal of dopamine inhibition of dopaminergic neurons of the ventral tegmental area is mediated by protein kinase C. Neuropsychopharmacology. 2012;37(2):543-56.
Nimitvilai, S., Arora, D. S., & Brodie, M. S. (2012). Reversal of dopamine inhibition of dopaminergic neurons of the ventral tegmental area is mediated by protein kinase C. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 37(2), pp. 543-56. doi:10.1038/npp.2011.222.
Nimitvilai S, Arora DS, Brodie MS. Reversal of Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area Is Mediated By Protein Kinase C. Neuropsychopharmacology. 2012;37(2):543-56. PubMed PMID: 21976045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of dopamine inhibition of dopaminergic neurons of the ventral tegmental area is mediated by protein kinase C. AU - Nimitvilai,Sudarat, AU - Arora,Devinder S, AU - Brodie,Mark S, Y1 - 2011/10/05/ PY - 2011/10/7/entrez PY - 2011/10/7/pubmed PY - 2012/4/18/medline SP - 543 EP - 56 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 37 IS - 2 N2 - Adaptation of putative dopaminergic (pDA) neurons in the ventral tegmental area (VTA) to drugs of abuse may alter information processing related to reward and reinforcement and is an important factor in the development of addiction. We have demonstrated that prolonged increases in the concentration of dopamine (DA) result in a time-dependent decrease in sensitivity of pDA neurons to DA, which we termed DA inhibition reversal (DIR). In this study, we used extracellular recordings to examine factors mediating DIR. A 40 min administration of DA (2.5-10 μM), but not the DA D2 receptor agonist quinpirole (50-200 nM), resulted in inhibition of neuronal firing followed by DIR. In the presence of 100 nM cocaine, inhibition followed by DIR was seen with much lower DA concentrations. Reversal of quinpirole inhibition could be induced by an activator of protein kinase C, but not of protein kinase A. Inhibitors of protein kinase C or phospholipase C blocked the development of DIR. Disruption of intracellular calcium release also prevented DIR. Reduction of extracellular calcium or inhibition of store-operated calcium entry blocked DIR, but the L-type calcium channel blocker nifedipine did not. DIR was age-dependent and not seen in pDA VTA neurons from rat pups younger than 15 days postnatally. Our data indicate that DIR is mediated by protein kinase C, and implicate a conventional protein kinase C. This characterization of DIR gives insight into the regulation of autoinhibition of pDA VTA neurons, and the resulting long-term alteration in information processing related to reward and reinforcement. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/21976045/Reversal_of_dopamine_inhibition_of_dopaminergic_neurons_of_the_ventral_tegmental_area_is_mediated_by_protein_kinase_C_ L2 - http://dx.doi.org/10.1038/npp.2011.222 DB - PRIME DP - Unbound Medicine ER -