Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats

Abstract

Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2-32 mg/kg IP) as well as idebenone (10-100 mg/kg IP) and physostigmine (0.1-0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.

Angiotensin II-Induced Pulmonary Edema in a Rabbit Model

“…This in vitro result is well-consis tent with previous in vivo results. These findings sug gest that the attenuating effect of minaprine on energy metabolism may play an important role in the amelio ration of behavioral deficits in a variety of ischemic models (4,5). At present, the mechanism of protection by minap rine is uncertain, and the precise mechanism should be clarified in the future.…”

Nootropic Candidates Inhibit Head-Twitches Induced by Mescaline in Mice.

“…produced a dose-de pendent reduction in the number of head-twitches in duced by s.c. injection of 100 mg/kg mescaline [F(3, 36) = 14.6, P < 0.01], an effect that reached signifi cance for the 32 and 100 mg/kg doses ( Table 1) In this study, the head-twitches induced by mescaline were inhibited by cholinesterase inhibitors such as THA, NIK-247 and physostigmine (6,7). Minaprine and nebracetam have been shown to act as agonists at M,-muscarinic receptors in the rat brain (8,9) and to reverse scopolamine-induced memory deficits in rats (10,11). Results of behavioral tests indicate that idebenone also has some cholinergic-activating action (12).…”

Working and Reference Memory in Rats in the Three-Panel Runway Task Following Dorsal Hippocampal Lesions.

“…The locations of the correct panel-gates were held constant within a ses sion, but were changed from one session to the next. Thus, twelve patterns of correct panel-gate locations were used in this experi ment, as described previously (10,11). In the reference memory task, three consecutive trials were given each day at 2-min intervals (one session).…”

“…We previously reported a new method for the study of learning and memory in rats, us ing a three-panel runway apparatus (10,11). In the present study, we investigated the ac quisition and retention of the runway perfor mance of rats with dorsal hippocampal lesions based on working and reference memory pro cedures.…”

“…Working and reference memory were assess ed by a three-panel runway apparatus (10,11). The apparatus (175 X 36 X 25 cm, length X width X height) is composed of a start box, a goal box, and four consecutive intervening choice points.…”