Activation of GABAergic Neurons in the Interpeduncular Nucleus Triggers Physical Nicotine Withdrawal Symptoms
BACKGROUND: Chronic exposure to nicotine elicits physical dependence in smokers, yet the mechanism and neuroanatomical bases for withdrawal symptoms are unclear. As in humans, rodents undergo physical withdrawal symptoms after cessation from chronic nicotine characterized by increased scratching, head nods, and body shakes.
RESULTS: Here we show that induction of physical nicotine withdrawal symptoms activates GABAergic neurons within the interpeduncular nucleus (IPN). Optical activation of IPN GABAergic neurons via light stimulation of channelrhodopsin elicited physical withdrawal symptoms in both nicotine-naive and chronic-nicotine-exposed mice. Dampening excitability of GABAergic neurons during nicotine withdrawal through IPN-selective infusion of an NMDA receptor antagonist or through blockade of IPN neurotransmission from the medial habenula reduced IPN neuronal activation and alleviated withdrawal symptoms. During chronic nicotine exposure, nicotinic acetylcholine receptors containing the β4 subunit were upregulated in somatostatin interneurons clustered in the dorsal region of the IPN. Blockade of these receptors induced withdrawal signs more dramatically in nicotine-dependent compared to nicotine-naive mice and activated nonsomatostatin neurons in the IPN.
CONCLUSIONS: Together, our data indicate that therapeutic strategies to reduce IPN GABAergic neuron excitability during nicotine withdrawal, for example, by activating nicotinic receptors on somatostatin interneurons, may be beneficial for alleviating withdrawal symptoms and facilitating smoking cessation.
This article reports the results of a low-intensity wraparound intervention, Maintaining Independence and Sobriety through Systems Integration, Outreach, and Networking (MISSION), to augment Treatment as Usual (TAU) and engage and retain homeless veterans with a co-occurring disorder (COD) in care. Using a quasi-experimental design, 333 homeless veterans were enrolled, 218 who received MISSION along with TAU and 115 who received TAU alone. Group assignment was based on MISSION treatment slot availability at time of enrollment. Compared with TAU alone, individuals receiving MISSION demonstrated greater outpatient session attendance within the 30 days before the 12-month follow up assessment and a larger decline from baseline in the number of psychiatric hospitalization nights. Individuals in the MISSION and TAU-only groups both showed statistically significant improvements in substance use and related problems at 12 months, with those in MISSION less likely to drink to intoxication and experience serious tension or anxiety. Although this study confirmed that compared with TAU alone, MISSION along with TAU is effective in augmenting usual care and engaging and retaining homeless veterans in treatment, some caution is warranted as this study did not involve random assignment. These results, however, are similar to a recent study involving a briefer version of the intervention which included random assignment. Based on these findings, MISSION is being further studied in the joint Department of Housing and Urban Development (HUD) - Department of Veterans Affairs (VA) Supportive Housing (HUD-VASH) program, which offers rapid housing placement and case management to aid in housing maintenance.
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OBJECTIVES: This pilot study examined the feasibility, preliminary efficacy, and determined the effect sizes of external qigong therapy (EQT) in reducing cue-elicited cocaine craving and associated symptoms among recently abstinent cocaine-dependent (CD) individuals.
METHODS: This study randomized 101 CD subjects to either a real EQT (n=51) or sham EQT control (n=50) group. Subjects underwent a baseline assessment and a weekly cue-exposure session for 2 weeks. Total EQT or sham treatments ranged from 4 to 6 sessions in 2 weeks.
RESULTS: EQT-treated subjects displayed a greater reduction in cue-elicited craving (p=0.06) and symptoms of depression (p<0.05) with medium effect sizes.
CONCLUSIONS: This study demonstrated the feasibility of delivering EQT among CD individuals early in residential treatment. Future research should include a larger sample and examine the mechanisms and potential longitudinal benefits of EQT.
Incremental efficacy of adding bupropion to the nicotine patch for smoking cessation in smokers with a recent history of alcohol dependence: results from a randomized, double-blind, placebo-controlled study
AIMS: The primary aim of this study was to compare the efficacy of smoking cessation treatment using a combination of nicotine patch and bupropion vs. nicotine patch and placebo bupropion. A secondary aim was to investigate whether the efficacy of bupropion is moderated by belief about whether one is receiving active or placebo medication.
METHODS: Participants were recruited from a residential substance abuse treatment program and the community. We randomly assigned 148 smokers with between 2 and 12 months of alcohol abstinence to nicotine patch plus bupropion or nicotine patch plus placebo. All participants also received seven counseling sessions.
RESULTS: At follow up, differences between medication conditions were not significant. Seven-day point prevalence quit rates in the patch plus bupropion vs. patch plus placebo conditions at week 24 were 6% and 11%, respectively. Differences between groups on prolonged abstinence and time to first smoking lapse were also not significant. However, among participants who received bupropion, those who accurately "guessed" that they were receiving bupropion were more likely to remain abstinent than those who incorrectly believed they were receiving placebo.
CONCLUSIONS: Findings do not support combining nicotine patch and bupropion for smoking cessation in this population. However, findings support previous studies suggesting the importance of assessing the blind in smoking cessation studies and its possible moderating effect on medication efficacy. Future directions for enhancing smoking cessation outcome in these smokers include investigations of intensive behavioral and pharmacological interventions, including studies of potential interactions between individual genetic differences and medication efficacy.
Impact of traumatic and violent victimization experiences in individuals with schizophrenia and schizoaffective disorder
Individuals with schizophrenia or schizoaffective disorder (SZ) experience more violent victimization and noninterpersonal traumatic experiences than the general population. Earlier studies, however, have generally excluded one or grouped together victimization and trauma experiences into single outcome variables, which may obscure their contributory role to SZ symptoms. This issue is important because there is some evidence that intentionally induced violence produces higher rates of psychopathology than nonintentional traumatic experiences. We examined the independent contribution of both types of victimization experiences on SZ patients' symptomatology. We were also interested in determining whether SZ patients' pattern of acute symptom presentation could discriminate between SZ patients with and without posttraumatic stress disorder (PTSD) comorbidity. SZ inpatients (n = 70) were assessed for the presence of comorbid PTSD diagnosis, violent victimization, and noninterpersonal traumatic experiences. Patients were also rated on SZ symptom severity and general psychopathology measures. Past violent victimization experiences predicted severity of dysphoria and anxiety in SZ. Past traumatic experiences, however, predicted severity of psychosis. Victimization predicted severity of patients' autistic/cognitive symptoms. SZ patients with comorbid PTSD presented with significantly more anxiety and dysphoria symptoms and SZ illness chronicity than their non-PTSD counterparts. Discriminant function analysis revealed that the severity of positive, dysphoric, autistic/cognitive, and anxiety symptoms differentiated comorbid PTSD patients from their non-PTSD counterparts, with an overall 72.9% classification rate. Past traumatic and victimization experiences are significantly associated with SZ patients' symptom severity and illness course in partially overlapping domains. Use of common assessment strategies may be employed to increase detection of PTSD in SZ patients presenting for acute treatment.