Oral Conditioned Cues Can Enhance or Inhibit Ethanol (EtOH)-Seeking and EtOH-Relapse Drinking by Alcohol-Preferring (P) Rats

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2016-04, Vol.40 (4), p.906-915
• Main Authors: Knight, Christopher P., Hauser, Sheketha R., Deehan Jr, Gerald A., Toalston, Jamie E., McBride, William J., Rodd, Zachary A.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Alcohol Drinking - prevention & control; Alcohol Drinking - psychology; Alcohol-Preferring (P) Rats; Animals; Conditioned Cues; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Cues; Drug-Seeking Behavior - drug effects; Drug-Seeking Behavior - physiology; Ethanol - administration & dosage; Ethanol-Relapse; Ethanol-Seeking; Female; Flavoring Agents - administration & dosage; Pavlovian Spontaneous Recovery; Rats; Reaction Time - drug effects; Reaction Time - physiology; Self Administration
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.13027

Background Conditioned cues can elicit drug‐seeking in both humans and rodents. The majority of preclinical research has employed excitatory conditioned cues (stimuli present throughout the availability of a reinforcer), but oral consumption of alcohol is similar to a conditional stimuli (presence of stimuli is paired with the delivery of the reinforcer) approach. The current experiments attempted to determine the effects of conditional stimuli (both excitatory and inhibitory) on the expression of context‐induced ethanol (EtOH)‐seeking. Methods Alcohol‐preferring (P) rats self‐administered EtOH and water in standard 2‐lever operant chambers. A flavor was added to the EtOH solution (CS+) during the EtOH self‐administration sessions. After 10 weeks, rats underwent extinction training (7 sessions), followed by a 2‐week home cage period. Another flavor was present during extinction (CS−). Rats were exposed to a third flavor in a non‐drug‐paired environment (CS0). EtOH‐seeking was assessed in the presence of no cue, CS+, CS−, or CS0 in the dipper previously associated with EtOH self‐administration (no EtOH available). Rats were maintained a week in their home cage before being returned to the operant chambers with access to EtOH (flavored with no cue, CS+, CS−, or CS0). Results The results indicated that the presence of the CS+ enhanced EtOH‐seeking, while the presence of the CS− suppressed EtOH‐seeking. Similarly, adding the CS− flavor to 15% EtOH reduced responding for EtOH while the CS+ enhanced responding for EtOH during relapse testing. Conclusions Overall, the data indicate that conditional stimuli are effective at altering both EtOH‐seeking behavior and EtOH‐relapse drinking. Alcoholic beverages have distinct flavors like mint, but these flavors are not specific to alcohol. Theories state that exposure to drug cues inadvertently, like mint toothpaste, promote craving and relapse. Study results indicate that flavors paired with alcohol trigger craving and relapse drinking. In contrast, flavors paired with the absence of alcohol block craving and relapse drinking. These findings indicate that relapse can be triggered by everyday events and establish neuropathways that with study will provide new treatments for addiction.