Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats.

Rationale: With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline.

Objectives: The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration.

Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats.

Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain. Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration.

Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects.

With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration.

Effects of Cohabitation on Neurodevelopmental Outcomes in Rats Discordant for Neonatal Exposure to Sevoflurane.

Background: Having a sibling with autism spectrum disorder is a risk factor for autism spectrum disorder. We used a rat model in which the general anesthetic sevoflurane (SEVO) induces autism spectrum disorder-like neurodevelopmental abnormalities to test whether they can be transmitted via cohabitation.

Methods: Male rat pups from several litters were mixed and randomized to 3 new litter types: SEVO-exposed (SEVO), SEVO-unexposed (control), and equal numbers of SEVO-exposed and SEVO-unexposed (MIXED).

Effects of systemic oxytocin receptor activation and blockade on risky decision making in female and male rats.

The neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment.

Enhanced cognitive flexibility and phasic striatal dopamine dynamics in a mouse model of low striatal tonic dopamine.

The catecholamine neuromodulators dopamine and norepinephrine are implicated in motor function, motivation, and cognition. Although roles for striatal dopamine in these aspects of behavior are well established, the specific roles for cortical catecholamines in regulating striatal dopamine dynamics and behavior are less clear. We recently showed that elevating cortical dopamine but not norepinephrine suppresses hyperactivity in dopamine transporter knockout (DAT-KO) mice, which have elevated striatal dopamine levels.

Sequencing hour-level temporal patterns of polysubstance use among persons who use cocaine, alcohol, and cannabis: A back-translational approach.

Background: Polysubstance use is highly prevalent among persons who use cocaine; however, little is known about how alcohol and cannabis are used with cocaine. We identified temporal patterns of cocaine+alcohol and cocaine+cannabis polysubstance use to inform more translationally relevant preclinical models.

Methods: Participants who used cocaine plus alcohol and/or cannabis at least once in the past 30 days (n=148) were interviewed using the computerized Substance Abuse Module and the newer Polysubstance Use-Temporal Patterns Section.

Effects of reproductive experience on cost-benefit decision making in female rats.

Many individuals undergo mating and/or other aspects of reproductive experience at some point in their lives, and pregnancy and childbirth in particular are associated with alterations in the prevalence of several psychiatric disorders. Research in rodents shows that maternal experience affects spatial learning and other aspects of hippocampal function. In contrast, there has been little work in animal models concerning how reproductive experience affects cost-benefit decision making, despite the relevance of this aspect of cognition for psychiatric disorders.

Neurobehavioral Abnormalities in Offspring of Young Adult Male Rats With a History of Traumatic Brain Injury.

Children of parents with traumatic brain injury (TBI) are more likely to develop psychiatric disorders. This association is usually attributed to TBI-induced changes in parents' personality and families' social environment. We tested the hypothesis that offspring of young adult male rats with TBI develop neurodevelopmental abnormalities in the absence of direct social contact with sires.

Cilia loss on distinct neuron populations differentially alters cocaine-induced locomotion and reward.

Background: Neuronal primary cilia are being recognized for their role in mediating signaling associated with a variety of neurobehaviors, including responses to drugs of abuse. They function as signaling hubs, enriched with a diverse array of G-protein coupled receptors (GPCRs), including several associated with motivation and drug-related behaviors. However, our understanding of how cilia regulate neuronal function and behavior is still limited.

Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome.

Limited long-term safety information exists for gabapentinoid treatment of idiopathic restless legs syndrome (RLS). We estimated incident mental health-related emergency department visits and hospitalizations with a primary mental health diagnosis (primary outcome) among early-onset idiopathic RLS patients following first-line treatment initiation and examined outcome risk with gabapentinoids compared with dopamine agonists (DAs). A retrospective cohort study was conducted using administrative claims data from 2012 to 2019.

Pharmacokinetics of delta-9-tetrahydrocannabinol following acute cannabis smoke exposure in mice; effects of sex, age, and strain.

Increased use of cannabis and cannabinoids for recreational and medical purposes has led to a growth in research on their effects in animal models. The majority of this work has employed cannabinoid injections; however, smoking remains the most common route of cannabis consumption. To better model real-world cannabis use, we exposed mice to cannabis smoke to establish the pharmacokinetics of Δ9THC and its metabolites in plasma and brain.

Effects of fentanyl self-administration on risk-taking behavior in male rats.

Rationale: Individuals with opioid use disorder (OUD) exhibit impaired decision making and elevated risk-taking behavior. In contrast to the effects of natural and semi-synthetic opioids, however, the impact of synthetic opioids on decision making is still unknown.

Objectives: The objective of the current study was to determine how chronic exposure to the synthetic opioid fentanyl alters risk-based decision making in adult male rats.

An ethogram analysis of cutaneous thermal pain sensitivity and oxycodone reward-related behaviors in rats.

Inter-relationships between pain sensitivity, drug reward, and drug misuse are of considerable interest given that many analgesics exhibit misuse potential. Here we studied rats as they underwent a series of pain- and reward-related tests: cutaneous thermal reflex pain, induction and extinction of conditioned place preference to oxycodone (0.56 mg/kg), and finally the impact of neuropathic pain on reflex pain and reinstatement of conditioned place preference.

Circuit and Cell-Specific Contributions to Decision Making Involving Risk of Explicit Punishment in Male and Female Rats.

Decision making is a complex cognitive process that recruits a distributed network of brain regions, including the basolateral amygdala (BLA) and nucleus accumbens shell (NAcSh). Recent work suggests that communication between these structures, as well as activity of cells expressing dopamine (DA) D2 receptors (D2R) in the NAcSh, are necessary for some forms of decision making; however, the contributions of this circuit and cell population during decision making under risk of punishment are unknown. The current experiments addressed this question using circuit-specific and cell type-specific optogenetic approaches in rats during a decision making task involving risk of punishment.

An ethogram analysis of cutaneous thermal pain sensitivity and oxycodone reward-related behaviors in rats.

Inter-relationships between pain sensitivity, drug reward, and drug misuse are of considerable interest given that many analgesics exhibit misuse potential. Here we studied rats as they underwent a series of pain- and reward-related tests: cutaneous thermal reflex pain, induction and extinction of conditioned place preference to oxycodone (0.56 mg/kg), and finally the impact of neuropathic pain on reflex pain and reinstatement of conditioned place preference.

Circuit and cell-specific contributions to decision making involving risk of explicit punishment in male and female rats.

Decision making is a complex cognitive process that recruits a distributed network of brain regions, including the basolateral amygdala (BLA) and nucleus accumbens shell (NAcSh). Recent work suggests that communication between these structures, as well as activity of cells expressing dopamine D2 receptors (D2R) in the NAcSh, are necessary for some forms of decision making; however, the contributions of this circuit and cell population during decision making under risk of punishment are unknown. The current experiments addressed this question using circuit- and cell type-specific optogenetic approaches in rats during a decision-making task involving risk of punishment.

Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury.

Background: The authors tested the hypothesis that the effects of traumatic brain injury, surgery, and sevoflurane interact to induce neurobehavioral abnormalities in adult male rats and in their offspring (an animal model of intergenerational perioperative neurocognitive disorder).

Methods: Sprague-Dawley male rats (assigned generation F0) underwent a traumatic brain injury on postnatal day 60 that involved craniectomy (surgery) under 3% sevoflurane for 40 min followed by 2.1% sevoflurane for 3 h on postnatal days 62, 64, and 66 (injury group).

Age-Related Changes in Risky Decision Making and Associated Neural Circuitry in a Rat Model.

Altered decision making at advanced ages can have a significant impact on an individual's quality of life and the ability to maintain personal independence. Relative to young adults, older adults make less impulsive and less risky choices; although these changes in decision making could be considered beneficial, they can also lead to choices with potentially negative consequences (e.g.

Dexmedetomidine Diminishes, but Does Not Prevent, Developmental Effects of Sevoflurane in Neonatal Rats.

Background: Sevoflurane (SEVO) increases neuronal excitation in neonatal rodent brains through alteration of gamma aminobutyric acid (GABA)(A) receptor signaling and increases corticosterone release. These actions may contribute to mechanisms that initiate the anesthetic's long-term neuroendocrine and neurobehavioral effects. Dexmedetomidine (DEX), a non-GABAergic α2-adrenergic receptor agonist, is likely to counteract SEVO-induced neuronal excitation.