Nicotine self-administration in rats: estrous cycle effects, sex differences and nicotinic receptor binding

Abstract

These results suggest that while males and females may regulate their intake of nicotine similarly under limited access conditions, the motivation to obtain nicotine is higher in females.

Sex differences in nicotine levels following repeated intravenous injection in rats are attenuated by gonadectomy

“…Research by Donny et al, 2000 did not report sex differences in arterial or brain levels following IV nicotine administration in rats that previously self-administered IV nicotine (i.e., 0.02, 0.06, or 0.09 mg/kg/injection) according to fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Although plasma and brain nicotine levels increased as a function of dose, no sex differences in arterial plasma or brain levels of nicotine were observed.…”

“…Sex is an important factor that mediates the neurobiological response to nicotine, and ultimately the course of dependence behavior in humans that abuse cigarettes. Basic science research has demonstrated nicotineinduced sex differences in rats by measuring various behavioral and non-behavioral indices (Rosecrans, 1971(Rosecrans, , 1972Battig, 1981;Grunberg et al, 1986;Levin et al, 1987;Kanyt et al, 1999;Booze, et al, 1999;Donny et al, 2000;Harrod et al, 2004;Chaudhri et al, 2005a), and epidemiological research strongly suggests sex differences in tobacco use and abuse (Waldron, 1991;Kandel et al, 1998;Westermeyer & Boedicker, 2000). Although there may be multiple factors which influence initiation and use of tobacco smoking, the neurobiological processes which mediate sex specific differences in response to nicotine are not well known.…”

Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement

“…The latter finding suggests that repeated response-dependent pairings between nicotine and a non-drug stimulus can enhance the reinforcing efficacy of the stimulus via Pavlovian conditioning, and subsequently increase its control over operant behavior. Removing the stimulus after animals have maintained responding for it during saline substitution causes a further decrease in lever pressing, providing additional support for this hypothesis (Cohen et al 2005;Caggiula et al 2001;Donny et al 2000). Finally, following extinction of responding induced by removing nicotine and concurrent non-drug stimuli, reinstatement of lever pressing can be stimulated by either priming infusions of nicotine (Chiamulera et al 1996;Shaham et al 1997;Andreoli et al 2003), or by presentations of a non-drug stimulus that was previously combined with nicotine (Caggiula et al 2001;Lesage et al 2004;Paterson et al 2005).…”

“…Second, the peak of the dose-response function in this condition is shifted to the right (0.06 mg/kg/inf; free base) relative to behavior reinforced by nicotine paired with a non-drug stimulus, where responding peaks at 0.02-0.03 mg/kg/inf (Corrigall and Coen 1989;Donny et al 2000;Donny et al 2003;Chaudhri et al 2005b). These data suggest that nicotine self-administration is less reliable in the absence of concurrent non-drug stimuli, and support the prior hypothesis that the primary reinforcing effects of nicotine alone are relatively weak.…”

“…Nicotine, like other drugs of abuse, is self-administered by a variety of animal species (Corrigall and Coen 1989;Goldberg et al 1981;Henningfield and Goldberg 1983a;Rose and Corrigall 1997). Nicotine self-administration is dose-and schedule-dependent (Corrigall and Coen 1989;Donny et al 2000;Shoaib et al 1997), extinguishes when nicotine is replaced with saline (Corrigall and Coen 1989;Shoaib et al 1997), and, in the absence of other reinforcing stimuli, is dependent on nicotine being response-contingent (Donny et al 1998). Models of nicotine self-administration are well established and have been used to investigate the behavioral, environmental and neurophysiological underpinnings of nicotine reinforcement (e.g., Caggiula et al 2001;Corrigall et al 1992;Picciotto et al 1998).…”