Louise Adermark

Background and Purpose: Nicotine dependence remains one of the leading causes of morbidity and mortality worldwide, with high relapse rates and post‐cessation weight gain representing persistent barriers to sustained abstinence. The incretin hormones glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) have emerged as novel treatment targets, as they appear to influence both reward‐related behaviours associated with addictive substances and body weight regulation. Whether recently developed multi‐receptor incretin agonists such as tirzepatide, a long‐acting dual GIP/GLP‐1 receptor agonist, affect nicotine‐induced behaviours remains unstudied. Experimental Approach: We investigated whether tirzepatide affects nicotine‐induced behaviours (locomotor stimulation and expression of locomotor sensitisation, expression and reinstatement of conditioned place preference) and related neurochemistry (in vivo microdialysis and ex vivo tissue neurochemical analysis) in male mice. Key Results: Tirzepatide attenuated nicotine‐induced locomotor stimulation in a dose‐related manner, and reduced nicotine‐induced place preference, and in vivo accumbal dopamine release. Furthermore, tirzepatide suppressed reinstatement of nicotine place preference and prevented the expression of locomotor sensitisation, indicating effects beyond acute reward processing. Ex vivo neurochemical analysis of addiction‐related brain regions in nicotine‐sensitised mice revealed that tirzepatide blocked nicotine‐induced dopamine elevations in the nucleus accumbens, ventral tegmental area and lateral septum. Furthermore, tirzepatide restored levels of multiple neurotransmitter systems, such as GABA, in a brain region‐specific manner, suggesting possible effects beyond dopaminergic signalling alone. Conclusions and Implications: Collectively, these findings indicate that tirzepatide attenuates nicotine‐induced locomotor stimulation and dopamine release, as well as the expression and reinstatement of place preference, and the expression of locomotor sensitisation, in mice.

Background: In Vietnam, smoking remains highly prevalent among people living with HIV (PLWH), posing significant health risks. As PLWH receiving HIV care represent a selected population that may differ from the general smoking population, evidence on the psychosocial factors shaping readiness to quit in this group remains limited. This study examines the associations between tobacco-related risk perception, self-efficacy, and social norms with advanced readiness to quit among PLWH who smoke and were enrolled in a smoking cessation trial in Vietnam. Methods: We conducted a secondary cross-sectional analysis of baseline data from the VQUIT randomized controlled trial, including 672 PLWH who currently smoked cigarettes some days or every day, recruited from 13 HIV outpatient clinics in Hanoi, Vietnam. Advanced readiness to quit was defined as currently trying to quit or planning to quit within 30 days; all other responses were classified as lower or no readiness. Multivariable logistic regression models with robust standard errors, clustered at the clinic level, were fitted to examine associations between risk perception, self-efficacy, four social norm constructs, and advanced readiness to quit. Results: Overall, 76.6% of participants reported advanced readiness to quit. Higher risk perception was consistently associated with increased odds of advanced readiness to quit (aORs ranged 1.10 to 1.13 across models). Injunctive norms (aOR=1.11, 95% CI: 1.03–1.20) and internalized norms (aOR=1.40, 95% CI: 1.02–1.94) were positively associated with advanced readiness to quit, while descriptive and subjective norms were not. Self-efficacy showed no significant association. Conclusion: Among PLWH enrolled in a smoking cessation trial in Vietnam, higher risk perception and stronger injunctive and internalized norms were associated with advanced readiness to quit. Cessation interventions integrated into HIV care may benefit from addressing both perceived smoking-related risks and norm-based motivations to quit.

Background: The use of non-combustible tobacco-free nicotine (TFN) products has increased markedly among adolescents. Although often perceived as less harmful than traditional tobacco products, nicotine use has been associated with psychological distress. Aim: This study examined whether TFN use is associated with symptoms of anxiety and depression in adolescents, whether these associations differ from those of traditional tobacco products, and whether gender identity affects the outcome. Methods: Adolescents aged 17 to 19 years were invited to complete an online questionnaire assessing nicotine use and psychological distress, measured using the Hospital Anxiety and Depression Scale (HADS). Data were analyzed using chi-square tests and logistic regression models. Results: A total of 3730 adolescents participated, of whom 30% reported nicotine use. TFN use was more common than tobacco use, while dual use was more prevalent among boys. Both TFN and tobacco use were associated with increased odds of anxiety or depression symptoms, with similar effect sizes across product types. However, association were partly gender-dependent. Among girls using nicotine, 80% reported anxiety symptoms, with higher frequency of use associated with greater risk. Among boys, nicotine use was associated with depressive symptoms, and dual product use was associated with an increased risk of psychological distress. Conclusion: Nicotine use is associated with psychological distress regardless of product type. Girls may be particularly vulnerable to anxiety-related symptoms, while dual use appears especially risky among boys. These findings highlight the need for gender-sensitive prevention strategies targeting dual use and the progression to regular nicotine use.

Alcohol use disorder (AUD) is a serious mental health condition and a risk factor for morbidity and preterm death. The drug acamprosate (Campral® – calcium-bis[N-acetylhomotaurinate]) is one of few pharmacological treatments available for AUD. Recent research suggests that the properties of acamprosate may be attributed to calcium, but the acute and long-term effects by calcium supplementation on ethanol-induced dopamine release and relapse-like drinking is not fully known. We used in vivo microdialysis and the alcohol deprivation model, to further define the interaction of local or systemic calcium and ethanol on accumbal dopamine and taurine levels, and to outline the impact of acute and repeated calcium treatment on dopamine and the alcohol deprivation effect (ADE) in male Wistar rats. The role of calcium was further studied by local administration of an L-type Ca ²⁺ channel (LTCC) blocker. The results demonstrate that acute local administration of calcium in naïve rats increased nucleus accumbens extracellular dopamine levels, and prevented ethanol from further increasing dopamine. In addition, the ethanol-induced elevation of taurine was delayed in animals receiving calcium. Following sub-chronic systemic calcium administration, the dopamine-elevating property of calcium was lost. The LTCC inhibitor nicardipine decreased accumbal dopamine levels and prevented both calcium and ethanol from altering dopamine output. Acute systemic calcium administration abolished the ADE in treatment-naïve rats, but not in rats pretreated with sub-chronic calcium. Taken together, the results suggest that acute properties of calcium abolish ethanol-induced effects within the mesolimbic dopamine system, while there is an indication of tolerance development to both the dopaminergic and behavioral ethanol-related effects of calcium, thus mimicking the outcomes previously observed with acamprosate.

Alcohol use disorder (AUD) is associated with a loss of control over alcohol use, putatively driven by maladaptive changes in neural circuitries, including the basolateral amygdala (BLA). The BLA, known for its role in emotional regulation and associative learning, contributes to the reinforcement of alcohol‐related behaviours, making it a critical target for understanding the underlying mechanisms of vulnerability to AUD. To further outline the role of BLA neurotransmission in AUD, we combined a multisymptomatic 0/3 criteria rodent model with electrophysiological whole‐cell recordings to identify the association between neurophysiological parameters in the BLA and vulnerability to AUD‐like progression. Our results demonstrate that when assessed after 4 months of voluntary alcohol consumption, rats can be subcategorized as resilient or vulnerable to AUD‐like behaviour. Electrophysiological recordings, performed directly after alcohol self‐administration, demonstrated that rats manifesting an AUD‐like vulnerable phenotype presented a reduced frequency and amplitude of spontaneous excitatory post‐synaptic currents (sEPSCs), indicating suppressed activation via glutamatergic inputs. Disinhibition induced by GABAA receptor antagonist did not differ between groups, and field potential recordings demonstrated reduced stimulus/response curves further supporting a hypoglutamatergic state. Additionally, the intrinsic excitability of BLA neurons was selectively decreased in vulnerable rats compared to both resilient and water control rats. Importantly, addiction score correlated with both synaptic transmission and intrinsic excitability of BLA neurons. Overall, our findings suggest that hypoexcitability of BLA neurons may represent a neurobiological underpinning that contributes to the development and persistence of alcohol addiction‐like behaviours following protracted alcohol exposure.

Alcohol use disorder is a severe mental health condition causing medical consequences and preterm death. Alcohol activates the mesolimbic dopamine system leading to an increase of extracellular dopamine (DA) in the nucleus accumbens, an event that is associated with the reinforcing effects of alcohol. Cholinergic interneurons (CIN) are important modulators of accumbal DA signalling, and depletion of accumbal CIN attenuates the alcohol‐induced increase in extracellular DA. The aim of this study was to explore the functional role of accumbal CIN in alcohol‐related behaviour. To this end, ablation of CIN was induced by local administration of anticholine acetyltransferase‐saporin bilaterally into the nucleus accumbens of male Wistar rats. Alcohol consumption in ablated and sham‐treated rats was studied using a two‐bottle‐choice intermittent alcohol consumption paradigm. Rats with depleted CIN consumed significantly less alcohol than sham‐treated controls. No differences in sucrose preference, motor activity, water intake or weight gain were noted between treatment groups, suggesting that the ablation selectively affected alcohol‐related behaviour. In conclusion, this study further supports a role for accumbal CIN in regulating alcohol‐consummatory behaviour.