SUMMARY Dopaminergic neurons in the ventral tegmental area (VTA) are well known for their role in mediating the positive reinforcing effects of drugs of abuse. Here, we identify in rodents and humans a population of VTA dopamine neurons co-expressing corticotropin releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates CRF mRNA in dopaminergic neurons of the posterior VTA, activates local CRF1 receptors, and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of CRF mRNA and specific pharmacological blockade of CRF1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal, and limited the escalation of nicotine intake. These results link the brain reward and stress systems within the same brain region in signaling the negative motivational effects of nicotine withdrawal.
Despite housing stability being a key concept in housing and homelessness policy, research, and service provision, it remains poorly defined and conceptualized, and to date there are no standard measures. We use in‐depth qualitative interviews with 51 young people transitioning away homelessness over the course of a year to examine the core dimensions of housing stability. Due to the potential for sudden change, we define housing stability as the extent to which an individual's customary access to housing of reasonable quality is secure. We define housing security among 8 main dimensions: housing type, recent housing history, current housing tenure, financial status, standing in the legal system, education and employment status, harmful substance use, and subjective assessments of housing satisfaction and stability. Based on these dimensions, we suggest a brief 13‐question scale that measures housing security.
Nicotine addiction is a worldwide epidemic that claims millions of lives each year. Genetic deletion of α5 nicotinic acetylcholine receptor (nAChR) subunits has been associated with increased nicotine intake, however, it remains unclear whether acute nicotine is less aversive or more rewarding, and whether mice lacking the α5 nAChR subunit can experience withdrawal from chronic nicotine. We used place conditioning and conditioned taste avoidance paradigms to examine the effect of α5 subunit-containing nAChR deletion (α5 -/-) on conditioned approach and avoidance behaviour in nondependent and nicotine-dependent and -withdrawn mice, and compared these motivational effects with those elicited after dopamine receptor antagonism. We show that nondependent α5 -/- mice find low, non-motivational doses of nicotine rewarding, and do not show an aversive conditioned response or taste avoidance to higher aversive doses of nicotine. Furthermore, nicotine-dependent α5 -/- mice do not show a conditioned aversive motivational response to withdrawal from chronic nicotine, although they continue to exhibit a somatic withdrawal syndrome. These effects phenocopy those observed after dopamine receptor antagonism, but are not additive, suggesting that α5 nAChR subunits act in the same pathway as dopamine and are critical for the experience of nicotine's aversive, but not rewarding motivational effects in both a nondependent and nicotine-dependent and -withdrawn motivational state. Genetic deletion of α5 nAChR subunits leads to a behavioural phenotype that exactly matches that observed after antagonizing dopamine receptors, thus we suggest that modulation of nicotinic receptors containing α5 subunits may modify dopaminergic signalling, suggesting novel therapeutic treatments for smoking cessation.
Despite several studies suggesting the therapeutic use of 5-hydroxytryptamine receptors type 2A (5-HT ) agonists in the treatment of substance use disorders, the neurobiological basis accounting for such effects are still unknown. It has been observed that chronic exposure to drugs of abuse produces molecular and cellular adaptations in ventral tegmental area (VTA) neurons, mediated by brain-derived neurotrophic factor (BDNF). These BDNF-induced adaptations in the VTA are associated with the establishment of aversive withdrawal motivation that leads to a drug-dependent state. Growing evidence suggests that 5-HT receptor signaling can regulate the expression of BDNF in the brain. In this study, we observed that a single systemic or intra-VTA administration of a 5-HT agonist in rats and mice blocks both the aversive conditioned response to drug withdrawal and the mechanism responsible for switching from a drug-naive to a drug-dependent motivational system. Our results suggest that 5-HT agonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal.
Background Healthcare systems have adopted different strategies to reduce the burden of cervical cancer. In Poland, a population-based screening program was implemented in 2006, leading to a downward trend in cervical cancer burden. However, screening rates are still low in relation to other EU member states. In Poland, Pap smears are mainly performed by gynecologists rather than Primary Health Care (PHC) physicians. Little is known about the experiences and attitudes of the latter regarding cervical cancer screening in a PHC setting. Methods A cross-sectional questionnaire-based survey was carried out among 43 PHC physicians from the Malopolska region in Poland. Barriers and attitudes towards cytology in a PHC setting were evaluated. Results Approximately 35% of surveyed physicians reported having experience in performing cytology. Almost 75% of PHC physicians lacked the necessary equipment in their office to perform the screening. None of the studied physicians performed Pap smears in their office at the time. The reasons included: shortage of competence (78.57%) and time (69.05%), the perception of Pap smears as a task for gynecologists (69.05%), the lack of financial incentives (61.90%), and the belief that their patients would be unwilling to undergo the test in their PHC physician’s office (33.33%). More than three quarters (76.74%) declared they would be ready to perform Pap smears if the tests were additionally paid. No significant associations between PHC physicians’ characteristics and their willingness to perform cytology screening were found. Conclusion The primary barrier to perform Pap smears by PHC physicians does not lie in their personal reluctance but in the organization of the healthcare system. Provision of required training and proper funding allocation can likely improve the screening rate of cervical cancer in Poland.
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