Novel in vitro perfusion system for the determination of hypothalamic–pituitary–adrenal axis responses

Moidel, Melissa A.; Belz, Emily E.; Czambel, R. Kenneth; Rubín, Robert T.; Rhodes, Michael E.

doi:10.1016/j.vascn.2005.10.001

Cited by 10 publications

(14 citation statements)

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“…Additional baseline culture medium samples were taken prior to each NIC administration. Following NIC stimulations at 70, 110 and 150 min, hormone concentrations returned to baseline by 100, 140, and 180 min, consistent with our earlier findings (Moidel et al, 2006). The duration of each experiment was 200 min (Fig 2).…”

Section: Methodssupporting

confidence: 92%

“…NIC, the main psychoactive component of cigarettes, has been shown to activate the HPA axis in a dose-dependent manner (Mendelson et al, 2005; Porcu et al, 2003; Rhodes et al, 2004; Rhodes et al, 2001a). Reports of sex differences in HPA axis responses to NIC are relatively few (e.g., (Faraday et al, 2005; Grota et al, 1997; Moidel et al, 2006; Pogun & Yararbas, 2009; Rhodes et al, 2004). Our previous in vivo studies indicate that NIC activates the HPA axis in a sexually diergic manner, males having significantly greater plasma AVP responses than females, and females having significantly greater plasma ACTH and CORT responses than males (Rhodes et al, 2001a).…”

Section: Introductionmentioning

confidence: 99%

“…We previously reported that, in a dynamic perfusion system of HPA tissues, NIC also activates the HPA axis in a sexually diergic manner (Moidel et al, 2006). However, only one NIC dose was used in the previous study and AVP was not measured.…”

Section: Introductionmentioning

confidence: 99%

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Sexually diergic, dose-dependent hypothalamic–pituitary–adrenal axis responses to nicotine in a dynamic in vitro perfusion system

McKlveen

Wilson

Rubín

et al. 2010

Journal of Pharmacological and Toxicological Methods

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Introduction The hypothalamic-pituitary-adrenal cortical (HPA) axis modulates physiological responses to stress. We previously reported sexually diergic, dose-dependent HPA responses in vivo following nicotine administration: Male rats had greater arginine vasopressin (AVP) responses than females, and female rats had greater adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than males. The goal of the present study was to further investigate sexually diergic, dose-dependent HPA responses following nicotine addition to an in vitro model of the HPA axis, so that hormone output could be determined at each level of the axis. Methods Hypothalami, pituitaries, and adrenal glands were harvested from male and female rats. One-half hypothalamus, one-half pituitary, and one adrenal gland were placed individually into three jacketed tissue baths connected by tubing and perfused in series with physiological medium. Sampling ports between tissue baths were used to collect buffer before and after addition of various doses of nicotine, for measurement of AVP and corticotropin-releasing hormone (CRH) from the hypothalamus bath, ACTH from the pituitary bath, and CORT from the adrenal bath. Hormones were measured by highly specific immunoassays. Results Stable temperatures, flow rates, pH, and hormone baselines were achieved in the in vitro system. Consistent with our in vivo and earlier in vitro studies, nicotine added to the hypothalamus tissue bath significantly increased HPA responses in a sex- and dose-dependent manner: Males had greater AVP responses than did females, and females had greater CRH responses than did males. Sexually diergic ACTH and CORT responses were less apparent and were higher in females. Discussion Our in vitro system accurately models in vivo HPA responses to nicotine in both sexes and thus represents a reliable method for investigating the effects of nicotine on components of the HPA axis. These studies may be pertinent to understanding the biological differences to NIC between men and women smokers.

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Section: Methodssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Sexually diergic, dose-dependent hypothalamic–pituitary–adrenal axis responses to nicotine in a dynamic in vitro perfusion system

McKlveen

Wilson

Rubín

et al. 2010

Journal of Pharmacological and Toxicological Methods

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“…For example, plasma corticosterone levels are increased to a greater extent in female versus male rats following repeated injections (Gentile et al, 2011; Moidel et al, 2006; Rhodes et al, 2001; 2004; Skwara et al, 2012) and continuous delivery (Faraday et al, 2005) of nicotine. In an in vitro perfusion system, the presence of nicotine increased CRF and ACTH levels to a greater extent in hypothalamic tissue that was collected from female versus male rats (Mcklveen et al, 2010; Moidel et al, 2006). Overall, these studies suggest that the behavioral and biological effects of nicotine on stress systems are greater in females as compared to males.…”

Section: Pre-clinical Research On the Long-term Effects Of Nicotinmentioning

confidence: 99%

A mechanistic hypothesis of the factors that enhance vulnerability to nicotine use in females

O’Dell

Torres

2014

Neuropharmacology

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Women are particularly more vulnerable to tobacco use than men. This review proposes a unifying hypothesis that females experience greater rewarding effects of nicotine and more intense stress produced by withdrawal than males. We also provide a neural framework whereby estrogen promotes greater rewarding effects of nicotine in females via enhanced dopamine release in the nucleus accumbens (NAcc). During withdrawal, we suggest that corticotropin-releasing factor (CRF) stress systems are sensitized and promote a greater suppression of dopamine release in the NAcc of females versus males. Taken together, females display enhanced nicotine reward via estrogen and amplified effects of withdrawal via stress systems. Although this framework focuses on sex differences in adult rats, it is also applied to adolescent females who display enhanced rewarding effects of nicotine, but reduced effects of withdrawal from this drug. Since females experience strong rewarding effects of nicotine, a clinical implication of our hypothesis is that specific strategies to prevent smoking initiation among females are critical. Also, anxiolytic medications may be more effective in females that experience intense stress during withdrawal. Furthermore, medications that target withdrawal should not be applied in a unilateral manner across age and sex, given that nicotine withdrawal is lower during adolescence. This review highlights key factors that promote nicotine use in females, and future studies on sex-dependent interactions of stress and reward systems are needed to test our mechanistic hypotheses. Future studies in this area will have important translational value toward reducing health disparities produced by nicotine use in females.

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“…Nicotine (NIC) administration increases HPA axis activity in both humans [1,43,44,51,64] and rodents [17,18,27,41,46,52,57,78]. Because there are few reports of sex differences in HPA axis responses to NIC [2,24,46,55,57,63], our laboratory’s focus has been to study sexual diergism (functional sex differences) in HPA axis responses to cholinergic stimulation [54,55,57,58,60]. We previously reported that NIC activated the HPA axis in a sexually diergic manner: NIC stimulated ACTH and CORT in female rats to a significantly greater degree than in male rats [46,55,57].…”

Section: Introductionmentioning

confidence: 99%

Sexually diergic hypothalamic–pituitary–adrenal (HPA) responses to single-dose nicotine, continuous nicotine infusion, and nicotine withdrawal by mecamylamine in rats

Gentile

Andrekanic

Karwoski

et al. 2011

Brain Research Bulletin

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Hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine (NIC) are sexually diergic: Female rats have higher adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses than do males. In the present study we determined HPA responses in male and female rats following single doses of NIC, a single-dose of NIC immediately following continuous NIC for two weeks, and NIC withdrawal by single-dose mecamylamine (MEC) following continuous NIC infusion for two weeks. Blood sampling occurred before and after MEC and NIC administrations for determination of ACTH and CORT. In accordance with our previous findings, female ACTH and CORT responses to single-dose NIC were greater than male responses. This sex difference remained after single-dose NIC followed continuous NIC infusion, but HPA responses in both sexes were significantly lower in magnitude and duration than in the single-dose NIC alone groups. Sex differences also were observed following NIC withdrawal by MEC: The HPA responses to pretreatment with MEC were significantly higher in magnitude and duration in the continuous NIC groups than in the single-dose NIC groups. These results demonstrate that HPA responses to NIC are reduced and transient following continuous NIC infusion but are enhanced and sustained following NIC withdrawal by MEC after continuous NIC, suggesting that NIC habituation and withdrawal influence the stress responses in a diergic manner. These findings highlight the importance of sex differences in the effect of NIC on HPA axis activity and stress responsiveness, which may have implications for directing NIC-addiction treatment specifically towards men and women.

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Novel in vitro perfusion system for the determination of hypothalamic–pituitary–adrenal axis responses

Cited by 10 publications

References 51 publications

Sexually diergic, dose-dependent hypothalamic–pituitary–adrenal axis responses to nicotine in a dynamic in vitro perfusion system

Sexually diergic, dose-dependent hypothalamic–pituitary–adrenal axis responses to nicotine in a dynamic in vitro perfusion system

A mechanistic hypothesis of the factors that enhance vulnerability to nicotine use in females

Sexually diergic hypothalamic–pituitary–adrenal (HPA) responses to single-dose nicotine, continuous nicotine infusion, and nicotine withdrawal by mecamylamine in rats

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