Nicotine blocks angiotensin II inhibition of LTP in the dentate gyrus.
Angiotensin (ANG)-containing axons, terminals, and receptors have been found in the hippocampus. When angiotensin II (ANG II) is administered to the dentate gyrus, long-term potentiation (LTP) induction, in response to medial perforant path stimulation, is inhibited and it can be blocked by losartan, an ANG II AT1 receptor antagonist. ANG II has been shown to mediate impairment of the retention of an inhibitory shock avoidance response and to be involved in ethanol and diazepam inhibition of dentate gyrus LTP, all of which can be blocked by losartan. Nicotine acetylcholine receptors are found in the hippocampus and nicotine is involved in the enhancement of complex and important psychological functions that are mediated by the hippocampus; therefore, the possibility that nicotine prevents the ANG II inhibition of dentate granule cell LTP was examined. Nicotine pretreatment reduced ANG II inhibition of LTP induction in a dose-dependent manner. Mecamylamine blocked the nicotine antagonism of ANG II-induced LTP inhibition and normal LTP occurred, whereas hexamethonium was ineffective in blocking these central effects of nicotine. Nicotine by itself did not affect normal LTP under these conditions. Nicotinic blocking of the ANG II inhibition of a frequency dependent type of synaptic plasticity provides a function for central nicotinic receptors and a possible mechanism of action a) to explain the enhancement of learning and memory by nicotine, b) an explanation for tobacco smoking while drinking alcohol, and c) a possible basis for the excessive use of tobacco in depression and schizophrenia that supports a possible therapeutic use of nicotine in some mental disorders.
Wayner
M J
MJ
Division of Life Sciences, University of Texas at San Antonio 78249-0662, USA.
Armstrong
D L
DL
Phelix
C F
CF
D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism*; D004336:Drug Antagonism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D009538:Nicotine