Biology subjects

Alonso-Caraballo, Y.

Publications and source records attributed to Alonso-Caraballo, Y..

5 recordsLinked to original sources

bioRxiv2025

Cocaine sensitization and accumbens shell plasticity depend on biological sex and gonadal hormones in C57BL/6J mice

Biological sex as a defining variable in drug sensitivity remains poorly understood. Here, we combine behavioral and electrophysiological analyses to examine the influence of sex and gonadal hormones on cocaine-induced psychomotor sensitization and nucleus accumbens shell (NAcSh) plasticity in the prominent C57BL/6J mouse strain. Males exhibited greater cocaine-evoked locomotor activity than females; castration attenuated responses, whereas ovariectomy enhanced them. This behavioral phenotype is opposite to what occurs in rats. A 10-14 day abstinence period abolished the sex difference in intact animals, and gonadectomy reduced cocaine-induced behavioral plasticity. Recordings from 309 medium spiny neurons revealed sex-dependent NAcSh plasticity. In males, cocaine decreased neuronal excitability, while in females it induced estrous cycle-dependent plasticity characterized by reduced excitability during diestrus relative to estrus. These effects were driven by cocaine-induced modulation of voltage-gated sodium channels. Cocaine potentiated glutamatergic strength in males but elicited estrous cycle-dependent depotentiation in females. These adaptations in excitability and glutamatergic strength were abolished by gonadectomy, and paralleled diminished behavioral plasticity during abstinence. These data illustrate that biological sex and hormonal milieu critically shape cocaine-induced plasticity, offering a more nuanced framework than the traditional notion of heightened female sensitivity to drugs of abuse.

neuroscience↗

bioRxiv2024

Wideband ratiometric measurement of tonic and phasic dopamine release in the striatum

Reward learning, cognition, and motivation are supported by changes in neurotransmitter levels across multiple timescales. Current measurement technologies for various neuromodulators (such as dopamine and serotonin) do not bridge timescales of fluctuations, limiting the ability to define the behavioral significance, regulation, and relationship between fast (phasic) and slow (tonic) dynamics. To help resolve longstanding debates about the behavioral significance of dopamine across timescales, we developed a novel quantification strategy, augmenting extensively used carbon-fiber Fast Scan Cyclic Voltammetry (FSCV). We iteratively engineered the FSCV scan sequence to rapidly modify electrode sensitivity within a sampling window and applied ratiometric analysis for wideband dopamine measurement. This allowed us to selectively eliminate artifacts unrelated to electrochemical detection (i.e., baseline drift), overcoming previous limitations that precluded wideband dopamine detection from milliseconds to hours. We extensively characterize this approach in vitro, validate performance in vivo with simultaneous microdialysis, and deploy this technique to measure wideband dopamine changes across striatal regions under pharmacological, optogenetic, and behavioral manipulations. We demonstrate that our approach can extend to additional analytes, including serotonin and pH, providing a robust platform to assess the contributions of multi-timescale neuromodulator fluctuations to cognition, learning, and motivation.

neuroscience↗

bioRxiv2024

Sex-specific behavioral and thalamo-accumbal circuit adaptations after oxycodone abstinence.

Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.

neuroscience↗

bioRxiv2021

Prenatal opioid exposure inhibits microglial sculpting of the dopamine system during adolescence

The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure. Microglia, the resident immune cells of the brain, respond to acute opioid exposure in adulthood. Moreover, microglia are known to sculpt neural circuits during healthy development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors (D1R) in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood in rats. This microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. However, virtually nothing is known as to whether this developmental program is altered by prenatal exposure to opioids. Here, we show in rats that maternal oxycodone self-administration during pregnancy leads to reduced adolescent microglial phagocytosis of D1R and subsequently higher D1R density within the NAc in adult male, but not female, offspring. Finally, we show that prenatal opioid exposure abolishes the extinction of oxycodone-conditioned place preference in these male offspring. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to long-term changes in neural systems and behavior. HighlightsO_LIPrenatal opioid exposure decreases offspring viability and body weight in males and females C_LIO_LIPrenatal opioid exposure decreases microglial phagocytosis of D1R in the nucleus accumbens in males only C_LIO_LIPrenatal opioid exposure increases nucleus accumbens dopamine D1 receptor expression in males but not females C_LIO_LIAdult males fail to extinguish oxycodone-conditioned place preference following prenatal oxycodone exposure C_LI

neuroscience↗

bioRxiv2019

Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens of female rats

Naturally occurring alterations in estradiol influence food intake in females. However, how motivational responses to food cues are affected by the estrous cycle or ovarian hormones is unknown. In addition, while individual susceptibility to obesity is accompanied by enhanced incentive motivational responses to food cues and increased NAc intrinsic excitability in males, studies in females are absent. Here, we examined basal differences in intrinsic NAc excitability of obesity-prone vs. obesity-resistant females and determined how conditioned approach (a measure of cue-triggered motivation), food intake, and motivation for food vary with the cycle in naturally cycling female obesity-prone, obesity-resistant, and outbred Sprague-Dawley rats. Finally, we used ovariectomy followed by hormone treatment to determine the role of ovarian hormones in cue-triggered motivation in selectively-bred and outbred female rats. We found that intrinsic excitability of NAc MSNs and conditioned approach are enhanced in female obesity-prone vs. obesity-resistant rats. These effects were driven by greater MSN excitability and conditioned approach behavior during metestrus/diestrus vs. proestrus/estrus in obesity-prone but not obesity-resistant rats, despite similar regulation of food intake and food motivation by the cycle in these groups. Furthermore, estradiol and progesterone treatment reduced conditioned approach behavior in obesity-prone and outbred Sprague-Dawley females. To our knowledge, these data are the first to demonstrate cycle- and hormone-dependent effects on the motivational response to a food cue, and the only studies to date to determine how individual susceptibility to obesity influences NAc excitability, cue-triggered food-seeking, and differences in the regulation of these neurobehavioral responses by the cycle.

neuroscience↗