Reinstatement of ethanol-seeking behavior following intravenous self-administration in Wistar rats.
BACKGROUND
In animal models of alcoholism, subjects are traditionally trained to self-administer ethanol via the oral route. However, ethanol is also self-administered intravenously (IV), a paradigm which offers several advantages over oral self-administration methods, including immediate delivery to the bloodstream, more rapid onset of pharmacological effects, and elimination of the need to utilize tastants or sweeteners to mask the aversive orosensory properties of ethanol. However, no studies to date have examined reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration.


METHODS
Male Wistar rats were implanted with indwelling jugular vein catheters and trained to self-administer ethanol IV (1% v/v solution, equivalent to 1 mg/kg) in an operant lever-pressing paradigm in twice daily 1 hour sessions. Each IV delivery of ethanol was paired with presentation of a light-tone complex stimulus. After stabilization of response patterns, IV self-administration behavior was subjected to extinction procedures. Next, animals were exposed to the three types of stimuli known to reinstate ethanol-seeking behavior: presentation of ethanol-associated cues, a priming dose of ethanol (0.5 g/kg i.p.), or exposure to stress via administration of the anxiogenic compound yohimbine (2.5 mg/kg i.p.) or its corresponding vehicle.


RESULTS
During the maintenance phase of self-administration, animals exhibited significantly more presses on the lever that delivered the ethanol solution than the inactive lever, indicating that IV ethanol functioned as a positive reinforcer. Following extinction, it was found that ethanol-seeking behavior could be reinstated by all three types of stimuli (cues, ethanol priming, and yohimbine). Vehicle injection did not affect responding on either lever.


CONCLUSIONS
Ethanol serves as a reinforcer when self-administered IV, and following extinction, ethanol-seeking behavior can be reinstated by ethanol-associated cues, ethanol priming, or a pharmacological stressor. Thus, reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration may be a novel animal model of relapse.
Gass
Justin T
JT
Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Olive
M Foster
MF
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012054:Reinforcement, Psychology; D012646:Self Administration
D002492:Central Nervous System Depressants; D000431:Ethanol