Pharmacological Manipulation of the Rostromedial Tegmental Nucleus Changes Voluntary and Operant Ethanol Self-Administration in Rats

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2016-03, Vol.40 (3), p.572-582
• Main Authors: Fu, Rao, Zuo, Wanhong, Gregor, Danielle, Li, Jing, Grech, Dennis, Ye, Jiang-Hong
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - drug therapy; Alcohol Drinking - psychology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - administration & dosage; Animals; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Ethanol - administration & dosage; Male; Microinjection; Microinjections; Muscimol; Muscimol - administration & dosage; Pedunculopontine Tegmental Nucleus - drug effects; Pedunculopontine Tegmental Nucleus - physiology; Rats; Rats, Long-Evans; Rodents; Self Administration; Stereotaxic Surgery; α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.12974

Background The aversive properties of ethanol (EtOH) that limit its intake are poorly understood. There is an increasing interest in the role of the rostromedial tegmental nucleus (RMTg), because it encodes aversion signals and inhibits motivated behaviors. It is also a major source of inhibitory GABAergic inputs to the midbrain dopamine neurons. Up to this time, the role of the RMTg in EtOH‐drinking behaviors has not been well explored. Methods Male Long–Evans rats were trained either to drink EtOH under the intermittent 2‐bottle‐choice protocol or to self‐administer EtOH in operant chambers under fixed‐ratio‐3 schedules. Changes in drinking behaviors induced by the bilateral infusion into the RMTg of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), an agonist of AMPA‐type glutamate receptors, or muscimol, an agonist of GABAA receptors, were measured. Results Consumption and preference for EtOH, numbers of active lever pressing, and head entrance to the EtOH port were all significantly decreased upon activation of the RMTg by the infusion of AMPA, but were increased upon inhibition of the RMTg by the infusion of muscimol. By contrast, intra‐RMTg infusion of these agents did not change sucrose consumption. Conclusions These data show for the first time that EtOH‐drinking and EtOH‐seeking behaviors of rats changed inversely with RMTg function, supporting the idea that the RMTg plays a crucial role in EtOH‐drinking behaviors. Cartoon demonstrating that intra‐RMTg infusion of AMPA or muscimol, which activates or inhibits the LHb, can decrease or increase, respectively, ethanol‐drinking and ethanol‐seeking behaviors without altering sucrose intake.