Nicotine administration stimulates the in vivo N‐methyl‐D‐aspartate receptor/nitric oxide/cyclic GMP pathway in rat hippocampus through glutamate release

Abstract

1 The in vivo e ects of nicotine on the nitric oxide (NO) synthase/cyclic GMP pathway of the adult rat hippocampus have been investigated by monitoring the levels of extracellular cyclic GMP during microdialysis in conscious unrestrained animals. 2 Intraperitoneal (i.p.) administration of nicotine caused elevation of cyclic GMP levels which was prevented by mecamylamine. The e ect of nicotine was abolished by local infusion of the NO synthase inhibitor N G -nitro-L-arginine (L-NOARG) or by the soluble guanylyl cyclase blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ). 3 Local administration of the NMDA receptor antagonists cis-4-(phosphonomethyl)-2-piperidinecarboxylic acid (CGS19755) and dizocilpine (MK-801) inhibited by about 60% the nicotine-induced elevation of cyclic GMP. Nicotine was able to stimulate cyclic GMP out¯ow also when administered directly into the hippocampus; the e ect was sensitive to mecamylamine, L-NOARG, ODQ or MK-801. 4 Nicotine, either administered i.p. or infused locally, produced augmentation of glutamate and aspartate extracellular levels, whereas the out¯ows of g-aminobutyric acid (GABA) and glycine remained una ected. Following local administration of high concentrations of nicotine, animals displayed symptoms of mild excitation (sni ng, increased motor and exploratory activity) during the ®rst 20 ± 40 min of infusion, followed by wet dog shake episodes; these behavioural e ects were prevented by mecamylamine or MK-801, but not by L-NOARG or by ODQ. 5 It is concluded that (a) nicotine stimulates the production of NO and cyclic GMP in the hippocampus; (b) this occurs, at least in part, through release of glutamate/aspartate and activation of NMDA receptors. Modulation of the NMDA receptor/NO synthase/cyclic GMP pathway may be involved in the cognitive activities of nicotine.

Chronic Oral Nicotine Normalizes Dopaminergic Function and Synaptic Plasticity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Primates

“…Changes in intracellular calcium probably represent an important initial event because nAChRs flux calcium and nAChR-evoked function is calcium dependent (O'Neill et al, 2002;Dajas-Bailador and Wonnacott, 2004;Quik, 2004;Wonnacott et al, 2005). Diverse downstream pathways and processes, such as phosphorylation, may be activated to lead to alterations in caspases, kinases, CREB (cAMP response element-binding protein), apoptotic signaling, the nitric oxide/cGMP pathway, and others (Fedele et al, 1998;Garrido et al, 2001;Brunzell et al, 2003;Mai et al, 2003;Jin et al, 2004).…”

Nicotine-Induced Norepinephrine Release in Hypothalamic Paraventricular Nucleus and Amygdala Is Mediated by N-Methyl-d-aspartate Receptors and Nitric Oxide in the Nucleus Tractus Solitarius

“…‫,ء‬ p Ͻ 0.05 or ‫,ءء‬ p Ͻ 0.01 compared with L-NAME (30)/Sal control group; #, p Ͻ 0.05 compared with KRB/Nic (0.065) treatment group; $, p Ͻ 0.05 compared with L-NAME (30)/Nic (0.065) group (n ϭ 4 -5 rats per cohort). tors and the subsequent activation of NMDA receptors (Fedele et al, 1998).…”

Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal

“…The records were later analyzed off-line by a person who was not familiar to the experiments. Dopamine-related behaviors, including sniffing, rearing, and locomotion, were distinguished (Fedele et al, 1998).…”

“…This data further indicated that the effects of saffron extract and safranal may at least partially mediate in the CNS. Dopamine-related behaviors have been postulated to be changed during stress (Fedele et al, 1998). These changes are the manifestations of the effects of CRF, polyopiomelanocortin (POMC), and corticosterone released during stress from the hypothalamus, pituitary, and adrenal gland, respectively (Koob, 2008).…”