Biology subjects

Ramos-Maciel, S.

Publications and source records attributed to Ramos-Maciel, S..

3 recordsLinked to original sources

bioRxiv2021

Sex-dependent changes in murine striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence

Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is known to be affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors, e.g., irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during withdrawal in a mouse chronic cannabis exposure model. Using a THC treatment regimen known to produce tolerance we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance inducing THC treatment. Sex differences were observed in nearly all metrics. Altered striatal DA release, sleep and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. To our knowledge these findings provide the first model of directly translatable non-precipitated cannabis withdrawal symptoms, in particular, sleep disruption.

neuroscience↗

bioRxiv2021

Environmental enrichment delays the development of stereotypic behavior and reduces variability in behavioral experiments using California mice (Peromyscus californicus).

Domesticated mice and rats have shown to be powerful model systems for biomedical research, but there are cases in which the biology of species is a poor match for the hypotheses under study. The California mouse (Peromyscus californicus) has unique physiological and behavioral traits and has emerged as a powerful model for studying sex differences in the biology of psychiatric disease, which is particularly relevant considering the new NIH guidelines that require the inclusion of sex as a biological variable. Despite its growing role in preclinical research, there is a lack of studies assessing species-specific housing needs, which presents a challenge for research facilities seeking to ensure good welfare and obtaining high-quality experimental data. Indeed, captive California mice present a high prevalence of stereotypic backflipping behavior, a common consequence of suboptimal housing and a potential source of experimental outcome variability. Using three different cage systems, the present studies show that increasing housing space as well as social and environmental complexity can delay the development of stereotypic behavior in male and female California mice. Critically, this reduction in stereotypy is accompanied by increased effect sizes of stress in an established model for social anxiety. These results suggest that increased cage size and enrichment could enhance welfare in California mice while simultaneously increasing the quality of behavioral experiments.

animal behavior and cognition↗

bioRxiv2020

Extra-hypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a social stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knock-down prevented stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naive mice increased social vigilance and reduced social approach. These results show that a population of extra-hypothalamic oxytocin neurons play a key role in controlling stress-induced social anxiety behaviors.

neuroscience↗