Fu R, Chen X, Zho W, Li J, Ye J-H (2014) Selective ablation of mu opioid receptor expressing gaba neurons in the rostromedial tegmental nucleus promotes ethanol intake. Neuroscience 2014 Abstracts 267.30. Society for Neuroscience, Washington, DC.
Summary: BACKGROUND AND PURPOSE The cellular mechanisms underlying the aversive effect of ethanol that limits its intake are not well understood, although recent evidence has linked aversion with synaptic inhibition of dopamine neurons in the ventral tegmental area. Emerging evidence indicates that the rostromedial tegmental nucleus (RMTg), a newly defined midbrain structure exerts a major GABAergic inhibitory control over midbrain dopamine neurons and encodes aversive stimuli. The RMTg contains mostly GABAergic neurons and with dense μ-opioid receptor (MOR) immunoreactivity. However, the role of RMTg in the regulation of ethanol intake has not been well investigated. EXPERIMENTAL APPROACH We compared voluntary ethanol intake and locomotion in rats with intra-RMTg infusion of dermorphin-saporin or blank saporin. Dermorphin-saporin is a neurotoxin, which could selectively lesion MOR-expressing neurons. We measured ethanol intake in rats given intermittent access to ethanol (20% vol/vol) using a two bottle choice paradigm. We euthanized the rats, dissected their brains and analyzed the glutamic acid decarboxylase67 (GAD67) and MOR protein expression and immunoreactivity immediately following the behavioral test. KEY RESULTS In rats that received intra-RMTg injection of dermorphin-saporin, we observed a robust increase in the intake of and the preference to ethanol, and in the locomotor activity; but a significantly reduced GAD67 and MOR protein expression, as well as a massive loss of neurons with GAD67 and MOR immunoreactivity within the RMTg. We observed no such changes in rats that received injection of blank saporin or saline. Together, These findings indicate that MOR-expressing GABA neurons in the RMTg play a crucial role in the regulation of ethanol consumption, implicating the dysfunction of these neurons likely play a critical role in the pathogenesis of alcoholism, and that these neurons should represent an appropriate target for the development of therapeutic strategies against alcohol use disorders.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)