title: Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcohol.
abstract: Repeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative-hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS-). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS- presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity.
authors.affiliation: Sussex Centre for Research in Alcohol, Alcoholism and Drug Dependence, School of Biological Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK. dns@biols.susx.ac.uk
authors.forename: D N
authors.initials: DN
authors.lastname: Stephens
authors.forename: G
authors.initials: G
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Duka
authors.forename: T L
authors.initials: TL
authors.lastname: Ripley
mesh_terms: D000161:Acoustic Stimulation; D020268:Alcohol-Induced Disorders, Nervous System / Q000150:complications* / Q000503:physiopathology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000209:etiology* / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000503:physiopathology
chemical_list: D000431:Ethanol