DARPP-32 Phosphorylation Opposes the Behavioral Effects of Nicotine

Role of Calcineurin in Nicotine-Mediated Locomotor Sensitization

“…Several drugs of abuse, including cocaine and nicotine, can increase phosphorylation of DARPP32 at the T34 site (Zhu et al, 2005;Lynch et al, 2006), and this phosphorylation appears to be critical for behavioral responses to cocaine (Zachariou et al, 2006). Although nicotine-mediated DARPP32 activation was not observed in the NAc in the current work, this may have resulted from tissue sampling that did not distinguish between core and shell subregions.…”

“…We therefore determined whether DARPP32 levels and phosphorylation state were altered in parallel with the behavioral response to nicotine. DARPP32 is phosphorylated as a result of dopamine receptor activation in the striatum and NAc (Greengard et al, 1999), and this phosphorylation can be modulated by nicotine administration (Hamada et al, 2004;Zhu et al, 2005). In the striatum, we observed an increase in levels of phospho-DARPP32 Thr 34 (pDARPP32 T34) after 40 d exposure to nicotine (F (3,29) ϭ 4.106; p ϭ 0.05, ANOVA) (Fig.…”

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

“…Indeed, in vivo administration of psychomotor stimulants, including nicotine, that promote dopamine release have been shown to increase DARPP-32 phosphorylation and activation of extracellular signalregulated kinase in a subset of striatal medium spiny neurons (Valjent et al, 2005). Nicotine increased the phosphorylation of striatal DARPP-32 at multiple sites in mice given systemic injections of nicotine (Zhu et al, 2005). In rat striatal slices in vitro, nicotine has been reported to modify DARPP-32 phosphorylation in a concentration-and time-dependent manner, by acting at ␤2* and ␣7 nAChRs (Hamada et al, 2004;Hamada et al, 2005).…”

Sex differences in response to nicotine in C57Bl/6:129SvEv mice

“…To examine sex differences in voluntary oral nicotine consumption, males and females were evaluated in the two-bottle choice paradigm across a range of nicotine concentrations for which reward or aversion has been reported ( Agatsuma et al, 2006 ;Lee et al, 2004 ;Zhu et al, 2005 ). Nicotine preference ratios revealed a reduced preference for nicotine (aversion) in males as nicotine concentration increased, whereas females consumed nicotine and water equally regardless of the nicotine concentration ( Figure 1 ).…”

“…This procedure measures directly the amount of nicotine consumed and enables investigators to distinguish direct nicotine effects from nicotineassociated cues, a prominent feature of the place-conditioning paradigm. Two-bottle choice has been reported to demonstrate both aversion and preference for nicotine in mice depending on nicotine concentration ( Adriani, Macri, Pacifi ci, & Laviola, 2002 ;Agatsuma et al, 2006 ;Klein, Stine, Pfaff, & Vandenbergh, 2003 ;Klein, Stine, Vandenbergh, Whetzel, & Kamens, 2004 ;Lee, Chen, Shih, & Hiroi, 2004 ;Meliska, Bartke, McGlacken, & Jensen, 1995 ;Robinson, Marks, & Collins, 1996 ;Zhu et al, 2005 ). In a twobottle choice paradigm, mice are exposed to two bottles: one containing water and the other nicotine, the locations of which are switched every few days to prevent conditioned place associations from masking drug effects ( Klein, 2001 ;Klein et al, 2004 ;Shaham, Alvares, Nespor, & Grunberg, 1992 ;Todte et al, 2001 ).…”