Effect of nicotine on cerebral blood flow in anesthetized rats

• Published in: Japanese Journal of Pharmacology Vol. 71; no. suppl.1; p. 175
• Main Authors: Uramoto, Hiroshi, Tani, Yoshihiro, Saito, Kyoshi, Ohno, Tomochika
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1996
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)36939-2

Nicotine exerts various pharmacological effects on the central and peripheral nervous systems. Recently, it has been reported that the pharmacological effects of some nicotinic agonists do not correlate with their affinity for nicotine binding sites. This pharmacological dilemma may be related to the multiplicity of nicotinic receptors. In the present study, we compared the effects of nicotine and various nicotinic acetylcholine receptor (nAChR) agonists on cerebral blood flow (CBF), blood pressure (BP), heart rate (HR) and hypoxia-induced amnesia, and also examined the mechanism of action in CBF. Cortical CBF measured by laser-Doppler flowmetry, BP and HR were continuously monitored in anesthetized rats. The hypoxic amnesia was produced in mice exposed to nitrogen gas for 35 sec, and examined using passive avoidance technique. (-)Nicotine (NIC) and ABT-418 (ABT) which reported selectively bound to alfa4-beta2 subunit of nAChRs, dose-dependently increased CBF and BP, and high doses of NIC (5mg/kg) and ABT (25mg/kg) decreased HR. Interestingly, at the low doses, NIC (0.2, 0.6mg/kg) and ABT (2mg/kg) significantly increased CBF, but not BP. (-)Cytisine (CYT： 1mg/kg) and (+/-)anabasine (5mg/kg) also increased CBF and BP transiently, but did not affect HR. The CYT-induced increase of CBF was significantly different from saline-control. However, (-)lobeline (LOB： 5mg/kg) and 1,1-dimethyl-4 phenyl-piperazinium (DMPP： 1mg/kg) did not influence CBF and HR, and LOB but not DMPP significantly decreased BP. NIC, ABT and CYT excerted anti-amnesic effect in terms of prolonged step-through latencies in hypoxic mice. Pretreatment with mecamylamine (centrally acting nAChR antagonist) completely inhibited the NIC-induced increase in CBF and BP, although the inhibitory effects of hexamethonium (peripheral acting nAChR blocker) and dPTry (Me) arginine vasopressin (AAVP; vasopressin antagonist) on NIC-induced CBF changes were weak as compared with mecamylamine. These findings suggest that CBF response to NIC is predominantly exerted via central nAChR, and correlated with anti-amnesic effect of NIC.