Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model

Sánchez, Victoria; Moore, Carl A.; Brunzell, Darlene H.; Lynch, Wendy J.

doi:10.1007/s00213-013-3359-3

Cited by 52 publications

(70 citation statements)

References 50 publications

(82 reference statements)

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“…This result substantiates our recent study of nicotine self-administration in Sprague-Dawley rats (Morganstern et al, 2013), and it is also consistent with other reports indicating that early exposure to a palatable, fat-rich diet increases ethanol drinking and enhances sensitivity to the locomotor-stimulating effects of another drug, amphetamine (Bocarsly et al, 2012; Cabanes et al, 2000). While somewhat lower than those described in certain studies (Bardo, Green, Crooks, & Dwoskin, 1999; Lynch, 2009; Sanchez, Moore, Brunzell, & Lynch, 2014), the levels of nicotine IV self-administration obtained in the present study are similar to those in other reports (Cohen, Koob, & George, 2012; Gilpin et al, 2014) as well as our previous publication (Morganstern et al, 2013). Our main new finding is that fat-exposed offspring exhibit increased responding to a mixture of nicotine and ethanol, an effect evident during the training period, the dose-response testing, and the progressive ratio testing.…”

Section: Discussionsupporting

confidence: 90%

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Karatayev

Lukatskaya

Moon

et al. 2015

Alcohol

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Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes an even greater vulnerability to the excessive co-use of nicotine and ethanol.

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Section: Discussionsupporting

confidence: 90%

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Karatayev

Lukatskaya

Moon

et al. 2015

Alcohol

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“…The notion that the rewarding effects of nicotine are greater in females is also supported in previous studies that compared sex differences in nicotine reward during the adolescent period of development. For example, adolescent female rats acquired nicotine IVSA at lower doses [28] and display higher levels of nicotine intake under extended access conditions [29] as compared to males. Another series of studies revealed that female rats that initiated nicotine IVSA during adolescence display an escalation of nicotine intake into adulthood, but this effect was not observed in males [30-31].…”

Section: Discussionmentioning

confidence: 99%

Estradiol promotes the rewarding effects of nicotine in female rats

Flores

Pipkin

Uribe

et al. 2016

Behavioural Brain Research

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It is presently unclear whether ovarian hormones, such as estradiol (E2) promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous selfadministration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day procedure involving 2 days of vehicle administration and 2 days of E2 administration. Two doses of E2 (25 or 250 ug) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06 mg/kg/0.1 ml). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2.

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“…In contrast to short-access schedules, long-access (23 hr) self-administration sessions can achieve levels of nicotine found in human smokers (Sanchez et al, 2014). However, nicotine is not the only tobacco constituent involved in addiction.…”

Section: Discussionmentioning

confidence: 99%

Nicotine self‐administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats

Vázquez-Sanromán

Monje²,

Bardo

2016

Addiction Biology

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Nicotine, a major psychoactive component of tobacco smoke, alters GABA modulation of dopamine (DA) neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self-administer IV nicotine (0.03 mg/kg/infusion) for 21 days in 1-h daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 min or 72 hr after the last session, immunofluorescence measurements for PNNs, PRV and c-Fos were conducted. In VTA, nicotine self-administration reduced the number of PRV+ cells surrounded by PNNs at 45 min, as well as reducing the intensity of PNNs, suggesting a remodeling of GABA interneurons in this region; the number of PRV+ cells surrounded by PNNs was also reduced at 72 hr. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC), but not in medial prefrontal cortex (PrL or IL), 45 min after the last session; PNNs were not detected in nucleus accumbens (shell or core). The reduction of PNNs in VTA and OFC was unrelated to c-Fos+ cells, as the percent of WFA+ cells co-expressing c-Fos was decreased in OFC, but not in VTA. Thus, nicotine self-administration remodeled PNNs surrounding GABA interneurons in VTA and its indirect connections to OFC, suggesting a new possible molecular target where nicotine-induced neuroplasticity takes place. PNN manipulations may prevent or reverse the different stages of tobacco addiction.

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Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model

Cited by 52 publications

References 50 publications

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Estradiol promotes the rewarding effects of nicotine in female rats

Nicotine self‐administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats

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