Up-Regulation of Brain Nicotinic Acetylcholine Receptors in the Rat during Long-Term Self-Administration of Nicotine: Disproportionate Increase of the α6 Subunit

Parker, Steven L.; Fu, Yongjian; McAllen, Kathleen; Luo, Jianhong; McIntosh, J. Michael; Lindstrom, Jon; Sharp, Burt M.

doi:10.1124/mol.65.3.611

Cited by 99 publications

(94 citation statements)

References 48 publications

(78 reference statements)

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“…Our laboratory and others have shown, using this prolonged access model (Valentine et al, 1997;Fu et al, 2001Fu et al, , 2003Brower et al, 2002;LeSage et al, 2002LeSage et al, , 2003LeSage et al, , 2006Parker et al, 2004), that adult rats will acquire nicotine SA in the absence of food deprivation or prior food-reinforced conditioning. For several reasons, this prolonged access model is advantageous for studying nicotine SA in rats during midadolescence.…”

Section: Adolescent Nicotine Self-administration H Chen Et Almentioning

confidence: 82%

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Chen

Matta

Sharp

2006

Neuropsychopharmacol

105

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As most human tobacco use begins during adolescence and ongoing development of the adolescent central nervous system could affect acquisition of nicotine self-administration (SA), our established rat SA procedure was modified to study adolescent acquisition of SA with prolonged access to nicotine (23 h/day). Postnatal age 43-45 female Lewis rats, without prior shaping, conditioning, or food deprivation, were housed in operant chambers equipped with two levers; pressing the active lever triggered an i.v. injection of nicotine. By the 10th day of SA, rats receiving 7.5, 15, 30, or 60 mg/kg/injection nicotine (free base) obtained 23716, 5078, 6578, or 4875 injections (mean7SE), respectively. In the 30 mg/kg/injection group, active : inactive ratio was greater than 2 after SA day 4; 92% of injections occurred during the 12-h active (dark) phase of the light cycle. Main effects (analysis of variance) were shown for day and lever (ie active vs inactive) (po0.001). Adolescent males showed similar dose-dependent nicotine SA. With the increasing workload imposed by raising the fixed ratio (FR), less nicotine was self-administered at FR 5 and 7 compared to FR 1 and 3. In comparison to adult females selfadministering 30 mg/kg/injection of nicotine at FR 1, adolescents acquired nicotine SA at an accelerated rate (po0.05) and received a greater number of injections (po0.05) by day 10. In conclusion, when given prolonged access to the drug, both female and male adolescent Lewis rats rapidly acquire nicotine SA within the dosage range and FR constraints previously observed in adult Lewis rats. However, adolescent females acquired the behavior more rapidly and attained higher levels of stable nicotine SA than adults.

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Section: Adolescent Nicotine Self-administration H Chen Et Almentioning

confidence: 82%

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Chen

Matta

Sharp

2006

Neuropsychopharmacol

105

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“…As reported previously (Brower et al, 2002;Parker et al, 2004;Valentine et al, 1997), SD and Lewis rats acquired nicotine (0.03 mg/kg) SA without prior training, priming or food deprivation when the drug was available 23 h/day. Similar levels of nicotine SA were achieved by the rats used throughout these experiments.…”

Section: Nicotine Samentioning

confidence: 84%

Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress

Chen

Sharp

2007

Neuropsychopharmacol

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We investigated the effect of chronic nicotine self-administration (SA) on hypothalamic-pituitary-adrenal (HPA) hormonal responses to acute stressors. Adult male Sprague-Dawley rats were given access to nicotine (0.03 mg/kg) for 23 h per day for 20 days. On day 1 of acquisition of nicotine SA, plasma levels of both adrenocorticotropin and corticosterone were significantly increased 15-30 min after the first dose of nicotine. These hormonal changes were no longer significant on day 3, when adrenocorticotropin levels were o60 pg/ml and corticosterone levels were o110 ng/ml during the hour after the first dose of nicotine. Chronic nicotine SA (20 days) significantly augmented (2-3-fold) both hormonal responses to mild foot shock stress (0.6 mA, 0.5 s per shock, 5 shocks per 5 min), but did not affect hormonal responses to moderate shock (1.2 mA, 0.5 s per shock, 5 shocks per 5 min), lipopolysaccharide or immobilization. Similar data were obtained in Lewis rats. These results provide further support for the concept that chronic nicotine SA is a stressor. In alignment with the effects of other stressors, nicotine activated the HPA axis on the first day of SA, but desensitization occurred with repeated exposure. Furthermore, chronic nicotine SA selectively cross-sensitized the HPA response to a novel stressor. These observations suggest that nicotine may selectively increase the HPA response to stressors in human smokers.

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“…Rodent studies have shown that intravenous nicotine self-administration leads to an increase in the number of α6* receptors in rats [114], but a decrease in the number of striatal α6* receptors in rodents chronically treated with nicotine by means of minipumps [115,116] or receiving it in drinking water [117]. These apparently discrepant results may be due to the different modalities of nicotine administration leading to differences in nicotine concentration in the brain and/or the kinetics or duration of receptor exposure, which may differently affect α6* nAChRs.…”

Section: Regulation Of Native Subtypes By Chronic Nicotine Exposurementioning

confidence: 99%

Structural and functional diversity of native brain neuronal nicotinic receptors

Gotti

Clementi

Fornari

et al. 2009

Biochemical Pharmacology

421

430

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Although some of the neural circuits involved in the acute and chronic effects of nicotine have been identified, much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions.We briefly review some recent findings concerning the structure and function of native nAChRs, focusing on the subtypes identified in the meso-striatal and habenulo-interpeduncular pathways, two systems involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the effect of chronic nicotine on the expression of native subtypes.

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Up-Regulation of Brain Nicotinic Acetylcholine Receptors in the Rat during Long-Term Self-Administration of Nicotine: Disproportionate Increase of the α6 Subunit

Cited by 99 publications

References 48 publications

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug

Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress

Structural and functional diversity of native brain neuronal nicotinic receptors

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