Biology subjects

Spodnick, M. B.

Publications and source records attributed to Spodnick, M. B..

3 recordsLinked to original sources

bioRxiv2022

Gestational day 12 moderate prenatal alcohol exposure produces sex-specific social impairments and attenuates prelimbic excitability and amygdala-cortex modulation of adult social behavior.

Lifelong social impairments are common in individuals with prenatal alcohol exposure (PAE), and preclinical studies have identified gestational day (G)12 as a vulnerable timepoint for producing social deficits following binge-level PAE. While moderate (m)PAE also produces social impairments, the long-term neuroadaptations underlying them are poorly understood. Activity of the projection from the basolateral amygdala to the prelimbic cortex (BLA[->]PL) leads to social avoidance, and the PL alone is implicated in negative social behaviors, making each of these potential candidates for the neuroadaptations underlying mPAE-induced social impairments. To examine this, we first established that G12 mPAE produced sex-specific social impairments lasting into adulthood. We then chemogenetically inhibited the BLA[->]PL using Clozapine N-Oxide (CNO) during adult social testing. This revealed that CNO reduced social investigation in control males, but had no effect on mPAE males or females of either exposure, indicating that mPAE attenuated the role of this projection in regulating male social behavior and highlighting one potential mechanism by which mPAE affects male social behavior more severely. Using whole-cell electrophysiology, we also examined mPAE-induced changes to PL pyramidal cell physiology and determined that mPAE reduced the excitability of these cells, likely due to increased suppression by inhibitory interneurons. Overall, this work identified two mPAE-induced neuroadaptations that last into adulthood and which may underlie the sexspecific vulnerability to mPAE-induced social impairments. Future research is necessary to expand upon how these circuits modulate both normal and pathological social behavior, and to identify sex-specific mechanisms leading to differential vulnerability in males and females.

neuroscience↗

bioRxiv2020

Adolescent intermittent ethanol exposure effects on kappa opioid receptor mediated dopamine transmission: Sex and age of exposure matter

Underage alcohol drinking increases the risk of developing alcohol use disorder (AUD). In rodents, adolescent ethanol exposure augments ethanol consumption and anxiety-like behavior while reducing social interaction. However, the underlying mechanisms driving these adaptations are not understood. The dopamine and kappa opioid receptor (KOR) systems in the nucleus accumbens (NAc) are implicated in affective disorders and AUD, with studies showing augmented KOR function and reduced dopamine transmission in ethanol-dependent adult animals. Thus, this study, we examined the impact of adolescent intermittent ethanol (AIE) exposure on dopamine transmission and KOR function. Rats were exposed to water or ethanol (4 g/kg, intragastrically) every-other-day during early (PD25-45) or late (PD45-65) adolescence. While AIE exposure during early-mid adolescence (early AIE) did not alter dopamine release in male and female rats, AIE exposure during late adolescence (late AIE) resulted in greater dopamine release in males and lower dopamine release in females. To determine the impact of AIE exposure on KOR function, we bath applied cumulative concentrations of KOR agonist, U50,488 (0.01-1.0 M), and measured its effect on dopamine release. Early AIE exposure potentiated KOR-mediated inhibition of dopamine release in female rats, while late AIE exposure attenuated this effect in male rats. Together these data suggest that AIE-exposure impact on neural processes is dependent on sex and exposure timing. These differences likely arise from differential developmental timing in males and females. This is the first study to show changes in KOR function following AIE exposure.

neuroscience↗

bioRxiv2020

Kappa-opioid receptor stimulation in the nucleus accumbens shell: Differential effects across the rostro-caudal axis on dopamine transmission and affective behavior

Neural circuit engagement within the nucleus accumbens (NAc) shell is implicated in the regulation of both negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote dysphoric behavior, while dopamine was viewed as interacting with reward behavior, and KOR activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have, separately, been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses. Whether or not this is due to interactions between KORs and dopamine, and if it extends to other affective behaviors, remains to be determined. In this study, we examined in rats the relationship between the KOR and dopamine systems in both the rostral and caudal NAc shell using ex vivo fast scan cyclic voltammetry and the impact of KOR activation on affective behavior using approach-avoidance assays. We report here that activation of KORs in the caudal NAc shell significantly inhibits dopamine release, stimulates novelty-induced rearing behavior, increases avoidance behavior, and reduces locomotor activity. In contrast, activation of KORs in the rostral NAc shell inhibits dopamine release to a lesser extent and instead increases approach behavior. Taken together, these results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and they suggest that this might be due to differences in KOR control over dopamine release.

neuroscience↗