Nicotinic acetylcholine receptor (nACh-R) agonist-induced changes in brain monoamine turnover in mice

Abstract

The aim of the present study was to evaluate the effects of nicotinic acetylcholine receptor (nACh-R) agonists such as (-)-nicotine and related compounds on brain monoamine turnover. A single administration of (-)-nicotine (0.04, 0.2, 1.0, and 5.0 mg/kg SC) increased both noradrenaline (NA) and dopamine (DA) turnover in a dose-dependent manner, and the maximum effects were achieved 30 min after treatment with (-)-nicotine (1.0 mg/kg). The effect of (-)-nicotine on serotonin (5-HT) turnover was complicated; 5-HT turnover was increased at a low dose of (-)-nicotine (0.04 mg/kg) but decreased at a high dose (1.0 mg/kg). The (-)-nicotine (1.0 mg/kg)-induced changes in monoamine turnover were blocked by pretreatment with the centrally acting nACh-R channel blocker mecamylamine (2.0 mg/kg i.p.) but not by hexamethonium (2.0 mg/kg i.p.). These findings indicate that systemically administered (-)-nicotine can enhance brain NA and DA turnover and affect 5-HT turnover, both of which are mediated by central nACh-R. The changes in the monoamine turnover induced by (+/-)-anabasine were similar to those induced by (-)-nicotine, while (-)-lobeline and (-)-cytisine had little effect, and 1,1-dimethyl-4-phenyl-piperazinium (DMPP) increased NA and 5-HT turnover but not DA turnover at all doses tested. (S)-3-Methyl-5-(l-methyl-2- pyrrolidinyl)isoxazole (ABT-418), a selective neuronal nACh-R agonist, increased NA, DA and 5-HT turnover, but had a weaker effect on DA turnover than NA and 5-HT turnover. In addition, 9-amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholine esterase inhibitor, also increased monoamine turnover in the brain. Pretreatment with mecamylamine completely blocked the THA-induced increase in NA and 5-HT turnover, but not in DA turnover, suggesting that the nACh-R system is involved in the THA-induced increase in brain NA and 5-HT turnover. On the other hand, (-)-cytisine, a partial agonist for the beta 2 subunit containing nACh-R, completely inhibited the nACh-R agonist- and THA-induced increases in NA turnover, but not in DA turnover, and normalized the changes in 5-HT turnover. In conclusion, the subtypes of nACh-Rs mediating DA turnover may be different from those mediating NA and 5-HT turnover in the CNS.

Nicotine (NC)-induced "depressive" behavioral symptoms and effects of antidepressants including cannabinoids (CBs)

“…However, unlike the IM group, the antidepressant drugs which inhibit the reuptake of monoamines (AT, CL, and FL) were not significantly effective in the NC group in the forced swimming test for these drugs could not be predicted based on the previous data and suggested a contribution of the monoamine system to the depression-related behavioral alterations in both forced swimming and tail suspension tests (Steru et al, 1985;Rénéric et al, 1998;Fujishiro et al, 2001). Nevertheless, considering the characteristic NC--tem in the forced swimming test, which include the alterations in dopamine levels (Tani et al, 1997;Renard et al, 2003), there seems to be a possibility that the antidepressants such as AT, CL and FL, which inhibit mainly the reuptake of noradrenaline and 5-hydroxy-tryptamine (5-HT), cannot antagonize effectively the NC-induced depressive swimming behaviors, at least during the test time, as compared to the other "antidepressant" drugs.…”

“…Although the detailed neuronal modifications correlated with the NC-suppressed swimming behaviors have not been elucidated, nAChR-mediated alterations in dopamine levels, etc. ), which can be caused characteristically by NC, have been demonstrated (Tani et al, 1997). Furthermore, even without any drug or stressor treatments, behavioral alterations during the forced swimming test, unlike the tail suspension test, have been reported to be accompanied immediately by rapid alterations in the brain monoamine levels (Renard et al, 2003).…”

Dopaminergic and cholinergic involvement in the discriminative stimulus effects of nicotine and cocaine in rats

“…The different effects of the three nicotinic agonists may relate to their different effects on dopamine transmission. Studies in vitro and in vivo suggest that common nicotinic mechanisms may be responsible for nicotine-and nornicotine-induced increases in dopamine (Grady et al 1992;Dwoskin et al 1993;Teng et al 1997), but lobeline may be different (Grady et al 1992;Clarke and Reuben 1996;Tani et al 1997). Terry et al (1998) suggested that lobeline might exhibit different receptor subtype selectivity compared with nicotine, or its effects may be via non-nicotinic mechanisms.…”

Depression-related anhedonic behaviors caused by immobilization stress: a comparison with nicotine-induced depression-like behavioral alterations and effects of nicotine and/or "antidepressant" drugs

“…2d). However, the effects of these antidepressant drugs were attenuated in the NC and IM-NC groups in the forced swimming test, which seemed to be correlated with the characteristic NC-induced nAChR--ver (Tani et al, 1997). Furthermore, in the forced swimming test, rapid alterations in brain monoamine levels have been reported even without any drug or stressor treatments (Renard et al, 2003), and thus there are postest itself may enhance the neuronal effects of NC and contribute to the attenuated effects of the antidepressant drugs related to monoamine reuptake.…”

“…Although there are several similarities in the neuronal responses (e.g. similar alterations in stress hormones and catecholamines) between the effects of IM and NC (Morse, 1989;Takahashi et al, 1998), the NC-induced characteristic depression-related behavioral and neuronal alterations, which were not observed in the IM treatment, have been reported in animal experimental models: occurrence of antidepressant-like effects at early time points (within 15 min) after repeated NC treatments, which is accompanied by early characteristic alterations in the interactions between nicotinic cholinergic and serotonergic systems (Tizabi et al, 1999;Vázquez-Palacios et al, 2004), and shorter duration (within 24 hr) of the NC-induced depression-like behavioral alterations in the forced swimming test as compared to the IM-induced behaviors, for which nicotinic acetylcholine receptor (nAChR)-mediated, rapid et al ., 1997;Hayase, 2007Hayase, , 2008.…”