Effects of Citalopram on Cue-Induced Alcohol Craving and Thalamic D2/3 Dopamine Receptor Availability.

BACKGROUND: Selective serotonin reuptake inhibitors are often used in alcohol use disorders. Clinical trials with selective serotonin reuptake inhibitors for alcohol use disorders, however, have yielded mixed results. The goal of this project was to assess whether a single i.v. dose of a selective serotonin reuptake inhibitor reduces craving for alcohol and/or simultaneously increases striatal dopamine concentration in individuals with alcohol dependence. METHODS: Alcohol-dependent (DSM-IV-TR criteria) volunteers and matched controls (n = 10/group) underwent a double-blind, placebo-controlled, within-subjects study. Participants received i.v. citalopram (40 mg) or saline (counter-balanced) followed by a cue-induced craving assessment and [18F]-fallypride positron emission tomography scanning. RESULTS: In the alcohol-dependent individuals, the citalopram (compared with saline) resulted in decreased cue-induced craving for alcohol. For the whole study group, cue-induced alcohol craving was inversely correlated with thalamic (but not striatal) dopamine D2/3 receptor availability. CONCLUSIONS: Acute serotonin reuptake inhibition reduces cue-induced alcohol craving. Furthermore, thalamic dopamine abnormalities and the striatal hyperdopaminergic hypothesis of alcohol use disorder are supported.

Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.

OBJECTIVE: To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. METHODS: Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4ß2* nicotinic cholinergic receptor binding using 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used. RESULTS: 2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p < 0.05, corrected cluster), but binding was not associated with cognition. The C group had significant inverse correlations between 2FA binding in the thalamus (left: rs = -0.55, p = 0.008; right: rs = -0.50, p = 0.02; N = 22) and hippocampus (left: rs = -0.65, p = 0.001; right: rs = -0.55, p = 0.009; N = 22) and the Trails A score. The AD group had inverse correlation between 2FA binding in anterior cingulate (left: rs = -0.50, p = 0.01; right: rs = -0.50, p = 0.01; N = 24) and Neurobehavioral Rating Scale agitation/disinhibition factor score. CONCLUSION: Cholinergic receptor binding is reduced in specific brain regions in mild to moderate AD and is related to neuropsychiatric symptoms. Among healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target.

Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use.

RATIONALE: Upregulation of α4ß2* nicotinic acetylcholine receptors (nAChRs) is one of the most well-established effects of chronic cigarette smoking on the brain. Prior research by our group gave a preliminary indication that cigarette smokers with concomitant use of caffeine or marijuana have altered nAChR availability. OBJECTIVE: We sought to determine if smokers with heavy caffeine or marijuana use have different levels of α4ß2* nAChRs than smokers without these drug usages. METHODS: One hundred and one positron emission tomography (PET) scans, using the radiotracer 2-FA (a ligand for ß2*-containing nAChRs), were obtained from four groups of males: non-smokers without heavy caffeine or marijuana use, smokers without heavy caffeine or marijuana use, smokers with heavy caffeine use (mean four coffee cups per day), and smokers with heavy marijuana use (mean 22 days of use per month). Total distribution volume (Vt/fp) was determined for the brainstem, prefrontal cortex, and thalamus, as a measure of nAChR availability. RESULTS: A significant between-group effect was found, resulting from the heavy caffeine and marijuana groups having the highest Vt/fp values (especially for the brainstem and prefrontal cortex), followed by smokers without such use, followed by non-smokers. Direct between-group comparisons revealed significant differences for Vt/fp values between the smoker groups with and without heavy caffeine or marijuana use. CONCLUSIONS: Smokers with heavy caffeine or marijuana use have higher α4ß2* nAChR availability than smokers without these drug usages. These findings are likely due to increased nicotine exposure but could also be due to an interaction on a cellular/molecular level.

Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis.

Patients with mild chronic inflammation of the rectum or ileum have reduced perceptual responses to rectosigmoid distension compared to patients with irritable bowel syndrome (IBS). The current study sought to identify differences in regional cerebral blood flow (rCBF) during rectal distension, which might correspond to these perceptual differences. In 8 male ulcerative colitis (UC) patients with quiescent disease, 7 male IBS patients and 7 healthy male controls, rCBF was assessed using 15O-water positron emission tomography at baseline and during actual and anticipated but undelivered rectal distensions. No group differences were seen in anterior insula and dorsal anterior cingulate cortex (dACC), two regions consistently activated by painful intestinal stimuli. However, IBS patients showed greater activation of the amygdala, rostroventral ACC, and dorsomedial frontal cortical regions. In contrast, no significant differences were observed between UC and controls. When these two non-IBS groups were combined, functional connectivity analyses showed that right lateral frontal cortex (RLFC) activation positively correlated with activation of the dorsal pons/periaqueductal gray, a key region involved in endogenous pain inhibition. According to the connectivity analysis, this effect was mediated by inhibition of medial frontal cortex by the RLFC. Chronic colonic inflammation is not necessarily associated with increased visceral afferent input to the brain during rectal distension. In the sample studied, the primary difference between functional and quiescent inflammatory disease of the colon was in terms of greater activation of limbic/paralimbic circuits in IBS, and inhibition of these circuits in UC and controls by the RLFC.