Administration of the 5HT3R agonists SR57227 (1-100 mu M) and m-chlorophenylbiguanide (mCPBG, 1-100 mu M) into the LC
increased NA in this nucleus (E-max = 675 +/- 121% and E-max = 5575 +/- 1371%, respectively) and decreased NA in the PFC (E-max = -49 +/- 6% and E-max = -25 +/- 11%, respectively). Administration of the 5HT3R antagonist Y25130 (50 mu M) into LC attenuated SR57227 effect in the LC (E-max = 323 +/- 28%) and PFC (E-max = -37 +/- 7%). The alpha 2ADR antagonist RS79948 (1 mu M) blocked the SR57227 effect in the PFC but it did not change the effect in the LC (E-max = 677 +/- 202%). In electrophysiological assays, both mCPBG (1-10 mu M) and SR57227 (1-10 mu M) reduced the firing S3I-201 order rate of about 50%
of tested LC neurons (maximal effect = -37 +/- 2% and -31 +/- LY3009104 in vivo 4%, respectively); this effect was partially blocked by Y25130 (50 mu M). Administration of RS79948 (1 mu M) reversed the inhibition induced by mCPBG. Competition radioligand assays against [H-3]UK14304 and [H-3]RX821002 (alpha 2ADR selective drugs) in the rat brain cortex showed a very weak affinity of SR57227 for alpha 2ADR, whereas the affinity of mCPBG for alpha 2ADR was 17-fold higher than that of SR57227 for alpha 2ADR. The present results suggest that 5HT3R stimulate NA release in the LC, which promotes simultaneously a decrease in the firing rate of LC neurons through alpha 2ADR and then a decrease of NA release in terminal areas such as the PFC. (C) 2012 Elsevier
Ltd. All rights reserved.”
“Rationale Impulsivity is related to greater risk of nicotine dependence, perhaps by enhancing sensitivity to nicotine’s reinforcing and rewarding effects during initial smoking experiences.
Objective We examined the influence of impulsivity characteristics on acute sensitivity to nicotine reward, reinforcement, and other effects in 131 young Digestive enzyme adult nonsmokers.
Materials adn methods Participants engaged in four sessions: the first three to assess dose-response effects of nasal spray nicotine (0, 5, 10 mu g/kg) on reward, as well as mood, physiological, and performance effects, and the fourth to assess nicotine reinforcement using a choice procedure. Five impulsivity factors, derived from factor analysis of self-report (e.g., Barratt Impulsivity Scale, Sensation-Seeking Scale, Novelty seeking) and computer (stop-go, delay discounting, probability discounting) measures of impulsivity, were labeled “”novelty seeking”", “”response disinhibition”", “”extraversion”", “”inhibition”", and “”probability/delay discounting”".
Results The associations of novelty seeking with nicotine reinforcement and reward tended to move in opposite directions by sex, generally being directly related in men but inversely or unrelated in women. Similarly, response disinhibition was associated with reward and some mood responses to nicotine that differed by sex.