Biphasic Effects of Nicotine upon Ecs-Induced Retrograde Amnesia in Mice
The effects of nicotine in (a) attenuating the amnesic effect of a post-conditioning electroconvulsive shock (ECS; G), (b) facilitating avoidance-response acquisition by isolation-housed mice (5), and (c) antagonizing the effects of stress effects upon memory (3) have suggested several biochemical substrates for those systems to which these actions relate. One hypothesis that has emerged from these studies is that the increased content of brain 5-hydroxytryptamine (5-HT), decrease in its turnover rate, and increase in its turnover time -as result from ECS (1, 2) can be maximally blocked by nicotine (6) given 45 min. before ECS and augmented when nicotine is administered I5 min. prior to ECS (2). O n the basis of previous behavioral findings I[ was further hypothesized that ECS-induced retrograde amnesia (which has been suggcstcd as being 5-HT-dependent) can be antagonized or potentiated depending upon [he time between nicotine treatment and a postconditioning ECS. Four groups of 30 CF-Is strain mice were given nicotine sulfate (1.0 mg.kg. i.p.) or 0.9% saline in an equivalent volume at either 15 or 45 min. prior to a single passive avoidance conditioning trial (4) followed within 10 sec. by a single transcorneal ECS (20 mA, 400 V, 200 msec.). Previous scudies (1, 2) have established that mice given no training reinforcement did not show acquisition or retention of the avoidance response and that in the absence of post-training ECS there was a high (-90%) incidence of response retention. All mice were tested for retention of the passive avoidance response 24 hr. after the training-ECS sequence. Saline-treated mice did not differ in the incidence of retrograde amnesia as a function of pre-ECS treatment time (x' = 0.11, p > 50); however, 80% of those mice treated with nicotine 45 min. before the training-ECS sequence showed criterion retention of the passive avoidance response, as compared with only 209% of the controls (x2 = 19.28, p < ,001). For the mice given nicotine 15 min. prior to [he training-ECS sequence, the incidence of conditioned response retention (10%) was less than that observed for controls (25%). Thus, the time between the administration of nicotine and ECS treatment after single-trial avoidance conditioning in mice is critical for determining whether the same dose of this drug antagonizes or potentiates the amnesic properties of such treatment. These findings are consistent with previous findings which indicate that the occurrence of rerrograde amnesia by post-training ECS depends upon alterations in cerebral 5-HT content and metabolism (2). The time course of the cerebral aminergic effens of nicotine (3) is consistent with the biphilsic requirements for temporally dependent interanion with the amnesic effect of ECS. REFERENCES 1. ESSMAN, W. B. Electroshock-induced retrograde amnesia and brain serotonin effects of several antidepressant compounds. Psychopharmacologia (Bedin), 1968, 13, 258-266.