Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors

Harrod, Steven B.; Mactutus, Charles F.; Bennett, Klark; Hasselrot, Ulla; Wu, Guanghan; Welch, M.A.; Booze, Rosemarie M.

doi:10.1016/j.pbb.2004.04.026

Cited by 71 publications

(78 citation statements)

References 48 publications

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“…Interestingly, nicotine can augment dopamine transporter function (Middleton et al, 2004) and density (Harrod et al, 2004), suggesting that enduring nicotine-induced alterations in dopamine transporter function and/or density may play a role in the enhanced effect of repeated methylphenidate following nicotine treatment.…”

Section: Discussionmentioning

confidence: 99%

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

Wooters

Neugebauer

Rush

et al. 2007

Neuropsychopharmacol

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Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

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Section: Discussionmentioning

confidence: 99%

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

Wooters

Neugebauer

Rush

et al. 2007

Neuropsychopharmacol

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…Research investigating the behavioral and neuropharmacological effects of repeated intravenous (IV) nicotine injection demonstrates sex differences in the expression of behavioral sensitization (Booze et al, 1999;Harrod et al, 2004;Harrod et al, 2006). Behavioral sensitization refers to an augmentation of a behavioral response following repeated administration of psychostimulant drugs (Downs and Eddy, 1932;Post, 1980;Post and Contel, 1983;Kalivas and Weber, 1988;Robinson and Berridge, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Behavioral sensitization refers to an augmentation of a behavioral response following repeated administration of psychostimulant drugs (Downs and Eddy, 1932;Post, 1980;Post and Contel, 1983;Kalivas and Weber, 1988;Robinson and Berridge, 2003). Studies examining nicotine-induced sex differences by passively administering nicotine via IV injection (50 μg/kg/injection) indicate that female rats exhibit increased behavioral sensitization of locomotor activity compared to males (Booze et al, 1999;Harrod et al, 2004). Sex differences in the expression of D 3 receptors and dopamine transporters (DAT) in the nucleus accumbens (N Acc) were also observed following repeated IV nicotine injection.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, females exhibited increased expression of D 3 receptors and decreased DAT in the N Acc relative to males; and there were no changes in the expression of D 1 or D 2 receptors in either sex. Multiple regression analyses suggest that D 3 receptors and DAT in various striatal and N Acc subregions differentially predicted nicotine-induced behaviors for males and females (Harrod et al, 2004). These findings demonstrate that repeated IV nicotine injections produce sex differences in the expression of behavioral sensitization, and suggest that nicotine-induced changes in D 3 receptors and DAT are, in part, responsible for increased behavioral sensitization in female rats.…”

Section: Introductionmentioning

confidence: 99%

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

Harrod

Booze

Mactutus

2007

Pharmacology Biochemistry and Behavior

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Previous research demonstrates that repeated intravenous (IV) nicotine injection resulted in increased locomotor sensitization in female relative to male rats. In order to determine if increased nicotine levels are detected in females compared to males the present experiment examined the plasma nicotine levels of male, female, castrated (CAST), and ovariectomized (OVX) rats (n = 7-11 rats/group) following repeated IV nicotine injection (50 μg/kg/injection). All rats received 14 IV nicotine injections, one/day. Approximately one minute after the 14th nicotine injection, rats were rapidly decapitated and trunk blood was collected immediately. Gas chromatography revealed a sex difference in nicotine content: higher plasma nicotine levels were measured from female rats (>10X increase) relative to males, and the sex difference was attenuated by gonadectomy. These data suggest that the sex difference in plasma nicotine levels is due to alteration in distribution or nicotine metabolism as a function of circulating gonadal hormones. These findings indicate that gonadal hormones may influence nicotine pharmacokinetics and therefore nicotine-induced sex differences in behavior.

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The Role of Nicotinic Receptors in the Attenuation of Autism‐Related Behaviors in a Murine BTBR T + tf/J Autistic Model

Mahmood

Aldhalaan²,

Alshammari

et al. 2020

Autism Research

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Nicotinic receptors are distributed throughout the central and peripheral nervous system. Postmortem studies have reported that some nicotinic receptor subtypes are altered in the brains of autistic people. Recent studies have demonstrated the importance of nicotinic acetylcholine receptors (nAChRs) in the autistic behavior of BTBR T + tf/J mouse model of autism. This study was undertaken to examine the behavioral effects of targeted nAChRs using pharmacological ligands, including nicotine and mecamylamine in BTBR T + tf/J and C57BL/6J mice in a panel of behavioral tests relating to autism. These behavioral tests included the three‐chamber social interaction, self‐grooming, marble burying, locomotor activity, and rotarod test. We examined the effect of various oral doses of nicotine (50, 100, and 400 mcg/mL; po) over a period of 2 weeks in BTBR T + tf/J mouse model. The results indicated that the chronic administration of nicotine modulated sociability and repetitive behavior in BTBR T + tf/J mice while no effects observed in C57BL/6J mice. Furthermore, the nonselective nAChR antagonist, mecamylamine, reversed nicotine effects on sociability and increased repetitive behaviors in BTBR T + tf/J mice. Overall, the findings indicate that the pharmacological modulation of nicotinic receptors is involved in modulating core behavioral phenotypes in the BTBR T + tf/J mouse model. Lay Summary The involvement of brain nicotinic neurotransmission system plays a crucial role in regulating autism‐related behavioral features. In addition, the brain of the autistic‐like mouse model has a low acetylcholine level. Here, we report that nicotine, at certain doses, improved sociability and reduced repetitive behaviors in a mouse model of autism, implicating the potential therapeutic values of a pharmacological intervention targeting nicotinic receptors for autism therapy. Autism Res 2020, 13: 1311–1334. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors

Cited by 71 publications

References 48 publications

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

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

The Role of Nicotinic Receptors in the Attenuation of Autism‐Related Behaviors in a Murine BTBR T + tf/J Autistic Model

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