Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolateral amygdala that project to the dorsal striatum

Nimitvilai-Roberts, Sudarat; Gioia, Dominic; Lopez, MF; Glaser, Christina M.; Woodward, John J.

doi:10.1016/j.neuropharm.2023.109463

Cited by 3 publications

(2 citation statements)

References 69 publications

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“…An increase in sEPSC frequency but no change in sEPSC amplitude is suggestive of presynaptic changes in glutamatergic transmission in both males and females following withdrawal from extended-access cocaine self-administration. It should be noted that the average sEPSC amplitude values observed here in the BLA are higher than some [30,31] but not other [32] previously reported amplitude values in this region in rodent studies. This may be due to differences in a variety of factors that can influence spontaneous excitatory transmission, including but not limited to: the age of the animals, the slicing plane (e.g., horizontal vs. coronal, which could lead to different intact circuits in slice), and the concentrations of extracellular and intracellular recording solutions.…”

Section: Cocaine Exposure Increases Bla Excitatory Synaptic Transmiss...contrasting

confidence: 82%

Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle

Corbett,

Miller,

Wannen

et al. 2023

Neuroendocrinology

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Introduction: Sex and ovarian hormones influence cocaine seeking and relapse vulnerability, but less is known regarding the cellular and synaptic mechanisms contributing to these behavioral sex differences. One factor thought to influence cue-induced seeking behavior following withdrawal is cocaine-induced changes in the spontaneous activity of pyramidal neurons in the basolateral amygdala (BLA). However, the mechanisms underlying these changes, including potential sex or estrous cycle effects, are unknown. Methods: Ex vivo whole cell patch clamp electrophysiology was conducted to investigate the effects of cocaine exposure, sex and estrous cycle fluctuations on two properties that can influence spontaneous activity of BLA pyramidal neurons: 1). Frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and 2). Intrinsic excitability. Recordings of BLA pyramidal neurons were conducted in adult male and female rats and across the estrous cycle following 2-4 weeks of withdrawal from extended-access cocaine self-administration (6h/day for 10 days) or drug-naïve conditions. Results: In both sexes, cocaine exposure increased the frequency, but not amplitude, of sEPSCs and neuronal intrinsic excitability. Across the estrous cycle, sEPSC frequency and intrinsic excitability were significantly elevated only in cocaine-exposed females in the estrus stage of the cycle, a stage when cocaine seeking behavior is known to be enhanced. Conclusions: Here we identify potential mechanisms underlying cocaine-induced alterations in the spontaneous activity of BLA pyramidal neurons in both sexes along with changes in these properties across the estrous cycle.

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Section: Cocaine Exposure Increases Bla Excitatory Synaptic Transmiss...contrasting

confidence: 82%

Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle

Corbett,

Miller,

Wannen

et al. 2023

Neuroendocrinology

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“…Various rodent models of alcohol exposure and consumption have shown sex-specific differences in the amounts of alcohol consumed, aversion resistance, alcohol seeking behaviors, magnitude and direction of alcohol-induced neuronal activity changes, and brain neuronal network adaptations ( Fulenwider et al, 2019 ; Xie et al, 2019 ; Nimitvilai et al, 2020 ; Alper et al, 2022 ; Leyrer-Jackson et al, 2022 ; Foo et al, 2023 ; Nimitvilai-Roberts et al, 2023 ; Sneddon et al, 2023 ). These differences are likely because of distinct neurophysiology and brain connectivity in males versus females.…”

Section: Discussionmentioning

confidence: 99%

Chemogenetic Perturbation of the Posterior But Not Anterior Cerebellum Reduces Voluntary Ethanol Consumption

Zamudio,

Gioia,

Glaser

et al. 2023

eNeuro

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The cerebellum communicates with brain areas critically involved in control of goal-directed behaviors including the prefrontal and orbitofrontal cortices and midbrain and basal ganglia structures. In particular, the posterior cerebellum is important for cognitive flexibility and has been implicated in alcohol and drug-related memory. We hypothesized that the cerebellum, through its multiple connections to reward-related brain circuitry, regulates alcohol consumption. To test this, we expressed inhibitory DREADDs (designer receptors exclusively activated by designer drugs) in molecular layer interneurons (MLIs) in anterior (IV-V) or posterior (VI-VIII) cerebellar lobules of male and female mice and activated them during alcohol drinking sessions. In a home-cage drinking paradigm, alcohol consumption was significantly decreased by clozapine-N-oxide (CNO) or deschloroclozapine (DCZ) administration in male mice expressing DREADDs in posterior but not anterior lobules. CNO/DCZ injections did not affect drinking in DREADD expressing female mice or in male mice expressing the control vector. Activation of DREADDs expressed in anterior or posterior lobules had no effect on sucrose or quinine consumption in male or female mice. During operant self-administration sessions, DCZ decreased the number of licks and bouts in male but not female mice expressing DREADDs in posterior lobules with no effect in control vector mice. Performance on an accelerated rotarod was unaffected by chemogenetic manipulation while distance travelled in the open field was decreased by DREADD activation in anterior but not posterior lobules. These results indicate that neuronal activity within the posterior cerebellar cortex plays an important role in the control of alcohol consumption in male mice.Significance StatementThe role of the cerebellum in regulating alcohol drinking behavior, independent from motor coordination, is largely unexplored. As cerebellar modulation of non-motor brain functions is localized primarily to posterior lobules, we chemogenetically perturbed cerebellar lobules to test their involvement in alcohol consumption. Chemogenetic manipulation of posterior lobules VI-VIII decreased alcohol consumption in male but not female mice and did not alter motor coordination and locomotion. Chemogenetic perturbation of the anterior cerebellum decreased locomotion in both male and female mice but had no effect on motor coordination or alcohol consumption. These findings suggest that in male mice, modulation of the posterior cerebellum may affect neuronal computation within basal ganglia, striatal and cortical regions known to be relevant in alcohol use disorders.

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Adolescent alcohol exposure modifies adult anxiety-like behavior and amygdala sensitivity to alcohol in rats: Increased c-Fos activity and sex-dependent microRNA-182 expression

Vázquez-Ágredos,

Valero,

Aparicio-Mescua

et al. 2024

Pharmacology Biochemistry and Behavior

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Chronic intermittent ethanol exposure differentially alters the excitability of neurons in the orbitofrontal cortex and basolateral amygdala that project to the dorsal striatum

Cited by 3 publications

References 69 publications

Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle

Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle

Chemogenetic Perturbation of the Posterior But Not Anterior Cerebellum Reduces Voluntary Ethanol Consumption

Adolescent alcohol exposure modifies adult anxiety-like behavior and amygdala sensitivity to alcohol in rats: Increased c-Fos activity and sex-dependent microRNA-182 expression

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