Reduced expression of ethanol sensitization by α3β4 nicotinic acetylcholine receptors in DBA/2J mice.

Miller, Carley N.; Kamens, Helen M.

doi:10.1037/pha0000324

Cited by 5 publications

(3 citation statements)

References 51 publications

(71 reference statements)

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“…The interactions between day and group are consistent with the experimental design and suggest that the pattern of activity across days is dependent on the experimental drug group. Thus, further analyses were limited to the key days that examined between-groups acute locomotor stimulation (Day 3) and sensitization (Day 11) ( Gubner et al, 2014 ; Miller and Kamens, in press ). On Day 3, the first day of morphine exposure in the chronic drug group, C57BL/6J mice showed increased locomotion in response to morphine injection compared to the chronic saline group that received saline, indicating the expected morphine stimulant response (main effect of drug group: F 1 , 22 = 24.4, p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

Adolescent Stress Reduces Adult Morphine-Induced Behavioral Sensitization in C57BL/6J Mice

Kamens

Miller

Caulfield

et al. 2021

Front. Behav. Neurosci.

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Deaths related to opioid use have skyrocketed in the United States, leading to a public health epidemic. Research has shown that both biological (genes) and environmental (stress) precursors are linked to opioid use. In particular, stress during adolescence–a critical period of frontal lobe development–influences the likelihood of abusing drugs. However, little is known about the biological mechanisms through which adolescent stress leads to long-term risk of opioid use, or whether genetic background moderates this response. Male and female C57BL/6J and BALB/cJ mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence and then tested for morphine locomotor sensitization or morphine consumption in adulthood. To examine possible mechanisms that underlie stress-induced changes in morphine behaviors, we assessed physiological changes in response to acute stress exposure and prefrontal cortex (PFC) miRNA gene expression. Adolescent stress did not influence morphine sensitization or consumption in BALB/cJ animals, and there was limited evidence of stress effects in female C57BL/6J mice. In contrast, male C57BL/6J mice exposed to adolescent CVSS had blunted morphine sensitization compared to control animals; no differences were observed in the acute locomotor response to morphine administration or morphine consumption. Physiologically, C57BL/6J mice exposed to CVSS had an attenuated corticosterone recovery following an acute stressor and downregulation of twelve miRNA in the PFC compared to control mice. The specificity of the effects for C57BL/6J vs. BALB/cJ mice provides evidence of a gene-environment interaction influencing opioid behaviors. However, this conclusion is dampened by limited locomotor sensitization observed in BALB/cJ mice. It remains possible that results may differ to other doses of morphine or other behavioral responses. Long-term differences in stress reactivity or miRNA expression in C57BL/6J mice suggests two possible biological mechanisms to evaluate in future research.

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Section: Resultsmentioning

confidence: 99%

Adolescent Stress Reduces Adult Morphine-Induced Behavioral Sensitization in C57BL/6J Mice

Kamens

Miller

Caulfield

et al. 2021

Front. Behav. Neurosci.

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“…The interactions between day and group are consistent with the experimental design and suggest that the pattern of activity across days is dependent on the experimental drug group. Thus, further analyses were limited to the key days that examined between-groups acute locomotor stimulation (Day 3) and sensitization (Day 11) (Gubner et al, 2014; Miller and Kamens, 2019). On Day 3, the first day of morphine exposure in the chronic drug group, C57BL/6J mice showed increased locomotion in response to morphine injection compared to the chronic saline group that received saline, indicating the expected morphine stimulant response (main effect of drug group: F 1,22 = 24.4, p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

Effect of Adolescent Stress on Adult Morphine-Induced Behavioral Sensitization is Dependent Upon Genetic Background

Kamens

Miller

Caulfield

et al. 2021

Preprint

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Deaths related to opioid use have skyrocketed in the United States, leading to a public health epidemic. Research has shown that both biological (genes) and environmental (stress) precursors are linked to opioid use. In particular, stress during adolescence – a critical period of frontal lobe development–influences the likelihood of abusing drugs. However, little is known about the biological mechanisms through which adolescent stress leads to long-term risk of opioid use, or whether genetic background moderates this response. Male and female C57BL/6J and BALB/cJ mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence (postnatal days, PND, 25-59) and then tested for morphine locomotor sensitization or morphine consumption in adulthood. To examine possible mechanisms that underlie stress-induced changes in morphine behaviors, we assessed physiological changes in response to acute stress exposure and miRNA gene expression in the prefrontal cortex. Male C57BL/6J mice exposed to adolescent CVSS had blunted morphine sensitization compared to control animals. No differences were observed in the acute locomotor response to morphine administration or morphine consumption in adult C57BL/6J mice. Stress did not influence morphine behaviors in BALB/cJ animals. C57BL/6J mice exposed to CVSS had a blunted corticosterone recovery following an acute stressor. Twelve miRNA were downregulated in the prefrontal cortex of C57BL/6J mice exposed to CVSS in adolescence, which suggests a biological mechanism through which stress may alter later morphine responses. The specificity of the effects for C57BL/6J versus BALB/cJ mice provides evidence of a gene by environmental interaction influencing opioid behaviors.

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“…Pedunculopontine tegmental, basolateral amygdala, and prefrontal cortical afferents to the VTA DA system, a system that plays a critical role in conditioned reward learning (Burns et al, 1993; Everitt and Robbins, 1992; Pears et al, 2003; Ranaldi, 2014), are severely impacted by CIE exposure (Arendt et al, 1988; Broadwater et al, 2018; Coleman et al, 2014; Jury et al, 2017; McGinnis et al, 2019; Morales et al, 2018; Pereira et al, 2019; Schindler et al, 2016; Vetreno et al, 2014). Also, there is evidence that repeated alcohol administration can cause long‐term sensitization associated with adaptive changes in midbrain DA neuronal output to and cholinergic signaling in the striatum (Miller and Kamens, 2019; Nestby et al, 1997; Tschumi et al, 2019; Xu and Kang, 2019). Therefore, if CIE exposure sensitizes the VTA DA neuronal system and affects signaling to this system—a system critical for mediating CS effects—then it would be expected that animals exposed to CIE might show differential responding to CSs compared to animals not exposed to CIE.…”

mentioning

confidence: 99%

Aberrations in Incentive Learning and Responding to Heroin in Male Rats After Adolescent or Adult Chronic Binge‐Like Alcohol Exposure

Galaj

Barrera

Morris

et al. 2020

Alcoholism Clin & Exp Res

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Background and Purpose: Binge drinking is a serious problem among adolescents and young adults despite its adverse consequences on the brain and behavior. One area that remains poorly understood concerns the impact of chronic intermittent ethanol (CIE) exposure on incentive learning.Methods: Here, we examined the effects of CIE exposure during different developmental stages on conditioned approach and conditioned reward learning in rats experiencing acute or protracted withdrawal from alcohol. Two or 21 days after adolescent or adult CIE exposure, male rats were exposed to pairings of a light stimulus (CS) and food pellets for 3 consecutive daily sessions (30 CS-food pellet pairings per session). This was followed by conditioned approach testing measuring responses (food trough head entries) to the CS-only presentations and by conditioned reward testing measuring responses on a lever producing the CS and on another producing a tone. We then measured behavioral sensitization to repeated injections of heroin (2 mg/kg/d for 9 days).Results: Adolescent and adult alcohol-treated rats showed significantly impaired conditioned reward learning regardless of withdrawal period (acute or prolonged). We found no evidence of changes to conditioned approach learning after adolescent or adult exposure to CIE. Finally, in addition to producing long-term impairments in incentive learning, CIE exposure enhanced locomotor activity in response to heroin and had no effect on behavioral sensitization to heroin regardless of age and withdrawal period.Conclusions: Our work sets a framework for identifying CIE-induced alterations in incentive learning and inducing susceptibility to subsequent opioid effects.

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Reduced expression of ethanol sensitization by α3β4 nicotinic acetylcholine receptors in DBA/2J mice.

Cited by 5 publications

References 51 publications

Adolescent Stress Reduces Adult Morphine-Induced Behavioral Sensitization in C57BL/6J Mice

Adolescent Stress Reduces Adult Morphine-Induced Behavioral Sensitization in C57BL/6J Mice

Effect of Adolescent Stress on Adult Morphine-Induced Behavioral Sensitization is Dependent Upon Genetic Background

Aberrations in Incentive Learning and Responding to Heroin in Male Rats After Adolescent or Adult Chronic Binge‐Like Alcohol Exposure

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