Morphine exposure during adolescence induces enduring social changes dependent on adolescent stage of exposure, sex, and social test.

Drug exposure during adolescence, when the "reward" circuitry of the brain is developing, can permanently impact reward-related behavior into adulthood. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that developmental changes in the nucleus accumbens reward region regulate social development in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day, P30-40) and preearly adolescence in females (P20-30). We thus hypothesized that the developmental stage of morphine exposure will differentially impact social behavior development such that drug administered during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Morphine exposure during adolescence induces enduring social changes dependent on adolescent stage of exposure, sex, and social test.

Drug exposure during adolescence, when the 'reward' circuitry of the brain is developing, can permanently impact reward-related behavior. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that social development occurs in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day (P)30-40) and pre-early adolescence in females (P20-30). We thus hypothesized that morphine exposure during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development.

Does Neuromodulation Reduce Chronic Pain Patient Emergency Department Utilization?

BACKGROUND: Chronic pain (CP) affects roughly 100 million adults in the United States. These subjects present disproportionately to the emergency department (ED). Neuromodulation (NM) has been shown to reduce ED visits longitudinally in subjects. OBJECTIVE: To compare ED utilization rates between subjects with CP with and without NM. METHODS: Subjects with failed back surgery syndrome, complex regional pain syndrome, or neuropathic pain diagnosis who visited the hospital between January 1, 2019, and December 31, 2019, were included. Subjects were divided into a NM-treated cohort and a non-NM cohort. Demographic information, medications, and pain provider visits were obtained. Pain-related ED visits between 2017 and 2019 were compared. RESULTS: A total of 2516 subjects were identified; 291 (11.6%) previously underwent NM. The non-NM cohort had significantly higher rate of pain-related ED visits compared with the NM cohort (15.1% vs 10.0%, P = .018). Younger age (odds ratio [OR] = 0.888 [0.843-0.935]), shorter distance to the hospital (OR = 0.807 [0.767-0.849]), lower household income (OR = 0.865 [0.831-0.901]), opioid use (OR = 1.375 [1.291-1.465]), nonopioid use (OR = 1.079 [1.033-1.128]), and non-NM therapy (OR = 1.751 [1.283-2.390]) were significant predictors of ED visits. Opioid use was the only significant predictor (OR = 6.124 [1.417-26.473]) associated with ED visits in the NM cohort. CONCLUSION: Subjects who underwent NM had fewer visits to the ED when compared with similar subjects who received conventional treatment. Opioid use prompted increased ED utilization in both cohorts. We posit that NM leads to improvement in pain outcomes, integration with multidisciplinary pain specialists, and reduction in severity and frequency of acute pain exacerbations, thereby limiting health care resource utilization.

Sex-Selective Effects on Behavior in a Mouse Model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that is caused by a mutation in either TSC1 or TSC2 TSC affects multiple systems of the body, and patients with TSC display a range of neurologic and behavioral manifestations including seizures, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder, anxiety, and mood disorders. Whereas behavioral phenotypes of many mouse models have been studied, the effects of sex have, for the most part, not been explored. We studied adult male and female Tsc2 heterozygous and control mice to investigate the influence of sex and genotype on behavior. On a test of social preference, Tsc2 heterozygous mice, regardless of sex, demonstrated lower preference for the stranger mouse than control mice. In the open field, Tsc2 heterozygous males and control females habituated to the open field with decreasing anxiety-like behavior over time, whereas Tsc2 heterozygous females did not show habituation to the open field environment. We did not find any statistically significant effects of genotype on open field activity, learning and memory or motor function. Our results highlight phenotype differences in Tsc2 heterozygous mice, some of which are influenced by sex. A consideration of how sex influences the behavioral phenotypes of TSC is critical to develop a more complete understanding of the disorder and better target future pharmacological treatments.