Opioid Use Disorders (OUDs) are of growing concern in the United States, as opioid related deaths have been increasing in recent years. Opioids are highly addictive and strengthen reward circuitry which makes it harder to stop their use. The area of the brain which is heavily involved in the reward circuitry is the ventral tegmental area (VTA) and has been the main area of research for studying the addiction pathway for many years. However, recent studies have shown a potential link between addiction and the cerebellum, which hasn’t been fully understood. Our study aims to explore this potential link between the cerebellum and addiction via the deep cerebellar nuclei (DCN), which have direct projections to the VTA. We have injected AAV virus into the DCN of mice which will express inhibitory designer receptor exclusively activated by designer drugs (DREADDs) activated by CNO or the control virus expressing mCherry only. As such all mice will be injected with the virus but only some will express DREADDs in their DCN neurons. The mice will then undergo morphine conditioned place preference (CPP), using a two chambered apparatus for four days and on the fifth day undergo a preference test. Our study predicts that mice which had their DCN neurons inhibited by CNO during the conditioning period will show less preference for the morphine side during their preference test, compared to control mice which had no DCN inhibition. Our study has the potential to provide evidence for the novel cerebellum's involvement in opioid addiction.

Deficits in executive function are well-documented in both animal models and individuals with Fetal Alcohol Spectrum Disorders (FASD). Cerebellar regions such as lobule VI and Crus I are key mediators of executive function and may be vulnerable to alcohol-induced damage. This study tested the hypothesis that binge-like ethanol exposure during the rodent equivalent of the human third trimester—postnatal day (P)6 in mice—leads to neuronal loss in these regions. We used two transgenic mouse strains: 1) Ai32(RCL-ChR2(H134R)/EYFP mice, which express channelrhodopsin-2/EYFP /EYFP/EYFP upon Cre recombinase activation (for future optogenetic studies), and 2) VGAT-Venus mice, which label GABAergic and glycinergic neurons with fluorescence, aiding cell identification. Mice received a single subcutaneous injection of ethanol (3.5 g/kg) or saline at P6 and were left undisturbed until adulthood. Immunohistochemical analysis of cryosectioned cerebellar tissue was used to assess neuronal density. Ai32 sections were stained with anti-calbindin antibodies (to label Purkinje neurons) and anti-NeuN antibodies (to label postmitotic neurons, particularly in the granule cell layer). Fluorescence imaging was performed using a Zeiss Axioscan Z1 at 20X magnification; analyses were conducted using Fiji (ImageJ). In Ai32 mice, no significant treatment effects were observed in the density of Purkinje or granule cells in lobule VI or Crus I, suggesting that ethanol-related executive function deficits occur without neuron loss in these regions. Ongoing analysis in VGAT-Venus mice aims to assess the selective vulnerability of inhibitory neurons. Future studies will investigate whether early alcohol exposure leads to persistent functional changes in cerebellar circuits critical for executive function.

Injection drug use (IDU) poses a wide range of health risks, yet the combined effects of overlapping conditions like brain injury (BI) and depression remain underexplored. BI, often resulting from accidents, assaults, or overdose-related events, may impair emotional regulation and cognitive functioning in persons who inject drugs (PWID). Depression is already prevalent among PWID, but it is unclear whether TBI intensifies this risk. This study explores whether the relationship between IDU and depression differs by a history of probable BI. Data for this study were collected as part of a larger study of Hispanic PWID living in Puerto Rico (Chiou et al., in press). All participants were screened for a history of IDU through self-report, visual inspection, and verified by urine sample. The history of probable BI was determined through a set of questions based on the Ohio State University-TBI Identification Method. Structured interviews were administered to collect information on participants’ substance use patterns, psychiatric symptoms, and demographics. Independent t-tests will be used to compare scores of psychiatric functioning between participants with and without probable BI. We expect that PWID with a history of probable BI will report higher levels of depression than those without. These findings may offer insight into how neural injury influences psychiatric outcomes in people who inject drugs and support future research on mental health disparities in underserved populations.

Motivation involves complex neural circuits, particularly within the midbrain and striatum, where neurotransmitters play significant roles in shaping reward-driven behavior. Recent studies suggest acetylcholine (ACh) release in the ventral tegmental area (VTA) as a key modulator of reward-seeking behavior. This study aims to investigate how manipulating ACh levels in the VTA during behavioral trials influences motivation toward natural rewards. To examine this, a series of behavioral paradigms were enacted, including reward consumption, Pavlovian conditioned reward-seeking, contextual renewal, and sensory-specific satiety. Pharmacological manipulations were used to alter cholinergic activity within the VTA. Twenty-three Long Evans rats (11 male, 12 female) were surgically implanted with cannula targeting the VTA to enable precise delivery of the following drugs. Rats received VTA infusions of either saline as a control, mecamylamine which blocks nicotinic receptors, physostigmine which increases ACh levels by inhibiting acetylcholinesterase, or scopolamine which blocks muscarinic receptors prior to testing. These treatments aim to isolate the contributions of specific cholinergic receptors on motivational processes. We expect that increasing ACh tone in the VTA will enhance motivation and reward-seeking and consumption, whereas blocking ACh signaling at muscarinic and nicotinic receptors will blunt reward-seeking. This research aims to fill a gap in understanding how cholinergic signaling within the midbrain contributes to motivational processes and how it may interact with dopaminergic systems in shaping reward-related behavior.