Work

Depression of substantia nigra dopamine transmission is driven by retrograde neurotensin release and is enhanced by methamphetamine self-administration

Year: 2019

Type: preprint

Abstract: Midbrain dopamine neurons play central roles in reward learning and motivated behavior, and inhibition at somatodendritic dopamine D2 receptor (D2R) synapses blunts psychostimulant reinforcement. Release of the neuropeptide neurotensin in the midbrain increases following methamphetamine exposure and induces long-term depression of D2R synaptic currents (LTD DA ), however the source of neurotensin that drives LTD DA is not known. Here we show that LTD DA is driven by neurotensin released by dopamine neurons. Optogenetic stimulation of dopamine neurons was sufficient to induce LTD DA in the substantia nigra, but not the ventral tegmental area, and was dependent on neurotensin receptors, postsynaptic calcium, and vacuolar-type H + -ATPase activity in the postsynaptic cell. Further, LTD DA was enhanced in mice that had self-administered methamphetamine. These findings reveal a novel form of signaling between dopamine neurons involving release of the peptide neurotensin, which may act as a feed forward mechanism to increase dopamine neuron excitability and methamphetamine self-administration.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/717843

Authors: Christopher W. Tschumi, Ramaswamy Sharma, William B. Lynch, Amanda L. Sharpe, Michael J. Beckstead

Institutions: Oklahoma Medical Research Foundation, The University of Texas at San Antonio Health Science Center, University of Oklahoma Health Sciences Center

Language: English

Topic: Neurotransmitter Receptor Influence on Behavior

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green