INDUCTION OF FOS-LIKE PROTEINS AND ULTRASONIC VOCALIZATIONS DURING ETHANOL WITHDRAWAL - FURTHER EVIDENCE FOR WITHDRAWAL-INDUCED ANXIETY

The ethanol withdrawal syndrome includes anxiety as a prominent sympto m. Because the extent that specific regions of brain are critical to t he generation of this emotional state is unknown, Fos-like immunoreact ivity (Fos-LI) was used to associate specific regions of the rat brain with the anxiety component of the ethanol withdrawal syndrome exacerb ated by an air puff challenge in rats. Chronic ethanol liquid diet was administered intragastrically for 4 days or by having the rats consum e the diet for 14 days, During withdrawal from either treatment protoc ol, Fos-LI was induced most prominently in forebrain areas, although t he midbrain and hindbrain were also represented, Included in these Fos -LI positive regions were many cortical regions, septum, accumbens, cl austrum, amygdala, paraventricular nucleus of the thalamus and hypotha lamus, hippocampus, locus coeruleus, and central gray. Fos-LI expressi on differed mostly in intensity between the two treatment and withdraw al protocols, with the gastric protocol producing the greatest Fos-LI induction in most brain regions. The threshold for air puff-induced ul trasonic vocalizations was decreased, and the number of vocalizations was increased and the period of vocalization was extended. These behav ioral data indicate that aversively motivated responding in rats durin g ethanol withdrawal can be readily quantified with the ultrasonic voc alizations test without precipitating convulsive activity, Furthermore , a comparison of the effects of the air puff challenge versus withdra wal on Fos-LI indicated that the behavioral state induced in these two situations share functional neuroanatomical features, Some regions-su ch as the accumbens core, medial septum, subregions of the amygdala, h ippocampus, substantia nigra, and cerebellum-exhibited little Fos-LI d uring withdrawal and also did not exhibit strong increases after the a ddition of the air puff challenge. However, other regions-such as the cerebral cortex (medial prefrontal, frontal, cingulate and ventrolater al orbital, claustrum, and tenia tecta), hypothalamus, and locus ceoru leus-exhibited Fos-LI at levels higher than that seen after either the ethanol withdrawal or puff challenge alone, These overlapping pattern s of Fos-LI in specific regions of the brain, activated by both ethano l withdrawal and an anxiety provoking behavioral challenge, suggest th at specific neuroanatomical sites in brain are associated with the sym ptom of anxiety observed during the ''ethanol withdrawal syndrome''.