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[Abstract Title]. - Society for Neuroscience

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either α7- (by methyllycaconitine, MLA) or α4β2-nAChRs (by dihydro-β-erythroidine, DHβE) 5<br />

min be<strong>for</strong>e nicotine exposure failed to prevent nicotine-induced increase in the AMPA/NMDA<br />

receptor ratio, but pretreatment with MLA and DHβE together abolished nicotine-induced<br />

increase in the AMPA/NMDA receptor ratio; (3) in both wild-type and nAChR β2 subunit<br />

knockout mice, a single injection (0.5 mg/kg, i.p.) of nicotine doubled the AMPA/NMDA<br />

receptor ratio; and (4) a single injection of nicotine reduced both the ratio of paired-pulseinduced<br />

glutamatergic responses and maximal evoked inhibitory postsynaptic current. These<br />

results suggest that either α7- or α4β2-nAChRs participate in mediation of systemic nicotinetreatment-induced<br />

increase in the AMPA/NMDA receptor ratio via activation of α7-containing<br />

nAChRs on glutamatergic terminals and by desensitization/down-regulation of α4β2-nAChRs on<br />

GABAergic neurons.<br />

Disclosures: J. Wu , None; M. Gao, None; R.J. Lukas, None.<br />

Poster<br />

258. Molecular and Neurochemical Basis of Nicotine Addiction<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm<br />

Program#/Poster#: 258.18/AA21<br />

Topic: C.16.k. Nicotine<br />

Support: Supported by an unrestricted grant from Philip Morris USA<br />

<strong>Title</strong>: Sazetidine-A selectively desensitizes alpha4beta2 nicotinic receptors and significantly<br />

reduces nicotine and cocaine self-administration in rats<br />

Authors: E. D. LEVIN 1 , D. HAMPTON 1 , S. SLADE 1 , M. CAULEY 1 , A. PETRO 1 , C.<br />

PERRAUT 1 , E. KHOLDEBARIN 1 , A. H. REZVANI 1 , Y. XIAO 2 , M. L. BROWN 3 , M. A.<br />

PAIGE 3 , B. E. MCDOWELL 3 , *K. J. KELLAR 2 ;<br />

1 Duke Univ. Med. Ctr., Durham, NC; 2 Dept Pharmacol, 3 Dept of Oncology, Georgetown Univ.<br />

Sch. Med., Washington, DC<br />

<strong>Abstract</strong>: Nicotine's effects on nicotinic cholinergic receptors (nAChRs) are crucial to the<br />

mechanisms underlying tobacco addiction, but one reason <strong>for</strong> less than optimal smoking<br />

cessation treatments is a poor understanding of these specific pharmacologic effects. In addition<br />

to its stimulatory actions on nAChRs, nicotine also markedly desensitizes these receptors. It is<br />

currently not known how much stimulation vs. desensitization each contribute to nicotine‟s<br />

varied behavioral effects. Sazetidine-A, a partial agonist at alpha4beta2 nAChRs, potently<br />

desensitizes these receptors. This study was conducted to determine if sazetidine-A would reduce<br />

nicotine self-administration (SA) in rats. After initial food pellet training and 10 sessions of

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