Effects of THA on passive avoidance retention performance of intact, nucleus basalis, frontal cortex and nucleus basalis + frontal cortex-lesioned rats.
Unilateral quisqualic acid lesions of the nucleus basalis magnocellularis (NBM) produced marked choline acetyltransferase depletion (-67% ipsilateral to lesion) and impaired passive avoidance (PA) retention at 24 hours. Pretraining injections of tacrine (THA: 1, 3 and 5 mg/kg), an anticholinesterase, failed to facilitate PA retention in intact rats. However, the retention performance of NBM-lesioned rats was improved by pretraining administration of THA at 3 mg/kg but not at either 1 or 5 mg/kg. Frontal cortex lesioning did not impair PA retention, and THA at 3 mg/kg had no effect on the PA retention of frontal cortex-lesioned rats. THA at 3 mg/kg failed to improve retention performance of NBM + frontal cortex-lesioned rats. After 10 days of chronic treatment with THA, NBM lesion-induced PA retention deficits were partially restored at both 3- and 5-mg/kg doses. The results suggest that 1) the insult to cholinergic neurons in the NBM may be involved in the PA memory consolidation deficit induced by nonselective quisqualic acid lesioning; 2) the beneficial effects of THA on NBM lesion-induced PA retention deficit occur in a narrow dose range; 3) the alleviating effects of THA on NBM lesion-induced PA memory deficits are blocked by frontal cortex lesions; and 4) the dose-response window for THA-induced PA retention performance improvement is broadened by repeated treatment.
Riekkinen
P
P
Department of Neurology, University of Kuopio, Finland.
Sirviö
J
J
Riekkinen
M
M
Riekkinen
P
P
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D016318:Quisqualic Acid / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013377:Substantia Innominata / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D013619:Tacrine / Q000494:pharmacology*
D013619:Tacrine; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase