Biology subjects

Glodosky, N. C.

Publications and source records attributed to Glodosky, N. C..

3 recordsLinked to original sources

bioRxiv2023

Sex differences in adolescent cannabis vapor self-administration mediate enduring effects on behavioral flexibility and prefrontal microglia activation in rats

Cannabis is the most used illicit drug in the United States. With many states passing legislation to permit its recreational use, there is concern that cannabis use among adolescents could increase dramatically in the coming years. Historically, it has been difficult to model real-world cannabis use to investigate the causal relationship between cannabis use in adolescence and behavioral and neurobiological effects in adulthood. To this end, we used a novel volitional vapor administration model to investigate long-term effects of cannabis use during adolescence on the medial prefrontal cortex (mPFC) and mPFC-dependent behaviors in male and female rats. Adolescent (35-55 day old) female rats had significantly higher rates of responding for vaporized {Delta}9-tetrahydrocannabinol (THC)-dominant cannabis extract (CANTHC) compared to adolescent males. In adulthood (70-110 day old), female, but not male, CANTHC rats also took more trials to reach criterion and made more regressive errors in an automated attentional set-shifting task compared to vehicle rats. Similar set-shifting deficits were observed in males when they were exposed to a non-contingent CANTHC vapor dosing regimen that approximated CANTHC self-administration rates in females. No differences were observed in effort-based decision making in either sex. In the mPFC, female (but not male) CANTHC rats displayed more reactive microglia with no significant changes in myelin basic protein expression or dendritic spine density. Together, these data reveal important sex differences in rates of cannabis vapor self-administration in adolescence that confer enduring alterations to mPFC structure and function. Importantly, female-specific deficits in behavioral flexibility appear to be driven by elevated rates of CANTHC self-administration as opposed to a sex difference in the effects of CANTHC vapor per se.

neuroscience↗

bioRxiv2022

Sex and timing of gonadectomy relative to puberty interact to influence weight, body composition, and feeding behaviors in mice

Gonadal sex steroids are important regulators of energy balance in adult rodents, and gonadectomy (GDX) has opposing effects on weight gain in sexually mature males and females. Puberty is associated with the emergence of sex differences in weight, body composition, and feeding behaviors, yet the role of gonadal hormones at puberty remains unclear. To address this, we performed GDX or sham surgery in male and female C57Bl/6 mice at postnatal day (P)25 (prepubertal) or P60 (postpubertal) timepoints and measured weight and body composition for 35 days, after which ad libitum and operant food intake was measured using Feeding Experimentation Device 3 (FED3s) in the home cage. Consistent with previous studies, postpubertal GDX caused weight gain in females and weight loss in males and increased adiposity in both sexes. However, prepubertal GDX decreased weight gain and altered body composition across the adolescent transition (P25 to P60) in males but had no effect in females. Despite the varied effects on weight, GDX decreased food intake and motivation for food as assessed in operant tasks regardless of sex or timing of surgery relative to puberty. Our findings indicate that GDX interacts with both sex and age at surgery to influence weight, body composition, and feeding behavior. HighlightsO_LIGonadectomy had opposing effects on weight in males and females when performed in adulthood. C_LIO_LIGonadectomy performed prior to puberty decreased weight gain in males but did not affect weight gain in females. C_LIO_LIAcross sex and age at surgery, GDX decreased ad libitum food intake and reduced operant responding for food. C_LIO_LIDecreased food intake under effortful conditions was not explained by body weight in GDX mice. C_LI

animal behavior and cognition↗

bioRxiv2019

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized {Delta}9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.

neuroscience↗