Activation of peroxisome proliferator-activated receptor γ reduces alcohol drinking and seeking by modulating multiple mesocorticolimbic regions in rats
- 1 July 2020
- journal article
- research article
- Published by Springer Nature in Neuropsychopharmacology
- Vol. 46 (2) , 360-367
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is an intracellular transcription factor whose signaling activation by the selective agonist pioglitazone reduces alcohol drinking and alcohol-seeking behavior in rats. The present study utilized the two-bottle choice and operant self-administration procedures to investigate neuroanatomical substrates that mediate the effects of PPARγ agonism on alcohol drinking and seeking in msP rats. Bilateral infusions of pioglitazone (0, 5, and 10 μg/μl) in the rostromedial tegmental nucleus (RMTg) decreased voluntary alcohol drinking and alcohol self-administration. Microinjections of pioglitazone in the ventral tegmental area (VTA), central amygdala (CeA), and nucleus accumbens (NAc) shell had no such effect. Notably, water, food, and saccharin consumption was unaltered by either treatment. The yohimbine-induced reinstatement of alcohol seeking was prevented by infusions of pioglitazone (0, 2.5, 5, and 10 μg/μl) in the CeA, VTA, and RMTg but not in the NAc shell. These results emphasize the involvement of mesocorticolimbic circuitries in mediating the effects of PPARγ agonists on alcohol drinking and seeking. These results will facilitate future studies that investigate the pathophysiological role of PPARγ in alcohol use disorder and help clarify the mechanisms by which the activation of this receptor decreases the motivation for drinking.Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (AA017447, AA017447)
- U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism
- MIUR, 2017
This publication has 59 references indexed in Scilit:
- Inhibitory Inputs from Rostromedial Tegmental Neurons Regulate Spontaneous Activity of Midbrain Dopamine Cells and Their Responses to Drugs of AbuseNeuropsychopharmacology, 2011
- The mesopontine rostromedial tegmental nucleus: An integrative modulator of the reward systemBasal Ganglia, 2011
- Neuronal circuits underlying acute morphine action on dopamine neuronsProceedings of the National Academy of Sciences, 2011
- Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosateNeuropsychopharmacology, 2011
- Drug-Evoked Synaptic Plasticity in Addiction: From Molecular Changes to Circuit RemodelingNeuron, 2011
- Role of Dorsal Medial Prefrontal Cortex Dopamine D1-Family Receptors in Relapse to High-Fat Food Seeking Induced by the Anxiogenic Drug YohimbineNeuropsychopharmacology, 2010
- Yohimbine Increases Impulsivity Through Activation of cAMP Response Element Binding in the Orbitofrontal CortexBiological Psychiatry, 2010
- Long-Evans Rats Acquire Operant Self-Administration of 20% Ethanol Without Sucrose FadingNeuropsychopharmacology, 2010
- The Rostromedial Tegmental Nucleus (RMTg), a GABAergic Afferent to Midbrain Dopamine Neurons, Encodes Aversive Stimuli and Inhibits Motor ResponsesNeuron, 2009
- The mesopontine rostromedial tegmental nucleus: A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compactaJournal of Comparative Neurology, 2009