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Ventral tegmental area GABA neurons and opiate motivation
Ryan Ting-A-Kee1, Hector Vargas-Perez, Jennifer K Mabey
1Institute of Medical Science, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada. r_kee@yahoo.com
Psychopharmacology
|February 9, 2013
Summary
Researchers found that inhibiting a specific ion transporter in the ventral tegmental area (VTA) can alter how morphine affects motivation, suggesting a new pathway for opiate addiction treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Opiate dependence alters morphine's motivational pathways from TPP-dependent to dopamine-dependent.
- Ventral tegmental area (VTA) GABAA receptors shift from hyperpolarizing to depolarizing during opiate withdrawal.
Purpose of the Study:
- To investigate if VTA GABAA receptor activity manipulation influences opiate motivation mechanisms.
- To explore the role of VTA GABA neurons in controlling opiate-driven motivation.
Main Methods:
- Used unbiased place conditioning in Wistar rats.
- Administered furosemide (Cl(-) cotransporter inhibitor) and acetazolamide (carbonic anhydrase inhibitor) intra-VTA.
- Performed electrophysiological recordings of mouse VTA GABA neurons.
Main Results:
- Intra-VTA furosemide induced a switch in morphine's motivational mechanisms, mimicking chronic opiate exposure.
- Acetazolamide prevented this behavioral switch.
- Furosemide reduced VTA GABA neuron sensitivity to muscimol and increased their firing rate.
Conclusions:
- Carbonic anhydrase may be part of a VTA GABA neuron pathway controlling opiate motivation.
- VTA GABAA receptor polarization (hyperpolarization vs. depolarization) selects TPP- or dopamine-dependent motivational outputs.
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