ABSTRACT
BACKGROUND: Most people agree that dependence to tobacco is mediated by the effects of nicotine on the central nervous system, albeit the neural pathways involved are not clearly delineated. We investigated the effect of nasal nicotine spray on regional cerebral blood flow (rCBF) in a sample of habitual smokers, with H2 15O and positron emission tomography (PET). METHODS: Eighteen volunteer smokers were studied after 12 hours of smoking deprivation. Regional cerebral blood flow measures were obtained with PET and 50 mCi H2 15O in six consecutive scans. Nicotine spray and a placebo spray were administered in a single-blind design, preceded and followed by baseline studies. Images were coregistered and anatomically standardized. Square (9-mm side) regions of interest were placed in 10 preselected brain regions, bilaterally. The effects of the experimental condition and gender were tested with two-way repeated-measures analysis of variance in each of the regions studied. RESULTS: Nicotine reduced rCBF in the left anterior temporal cortex and in the right amygdala. Increases were noted in the right anterior thalamus. CONCLUSIONS: In habitual smokers after overnight abstinence, nicotine induced differing effects on regional blood flow relative to whole brain blood flow. Increases were observed in the thalamus, a region rich in nicotinic receptors, and reductions in limbic and paralimbic (amygdala, anterior temporal cortex) regions.
Subject(s)
Brain/blood supply , Brain/drug effects , Circadian Rhythm , Nicotine/adverse effects , Smoking , Adolescent , Adult , Cerebrovascular Circulation/drug effects , Cotinine/blood , Female , Humans , Male , Middle Aged , Nicotine/blood , Substance Withdrawal Syndrome/etiology , Temporal Lobe/blood supply , Temporal Lobe/drug effects , Thalamus/blood supply , Thalamus/drug effects , Tomography, Emission-ComputedABSTRACT
A principle of opioid pharmacotherapy is that high medication doses should occupy fractionally more opioid receptors that mediate heroin effects. In this preliminary study we examined in vivo mu opioid receptor (muOR) binding in three healthy opioid-dependent volunteers during maintenance on 2 and 16 mg sublingual buprenorphine (BUP) liquid, and after detoxification (0 mg) under double-blind, placebo-controlled conditions, and once in matched controls. Binding measures were obtained with the muOR-selective radioligand [11C]carfentanil (CFN) and PET 4 hrs after BUP administration. BUP induced dose-dependent reductions in muOR availability, 36-50% at 2 mg and 79-95% at 16 mg relative to placebo. Heroin abusers also had greater muOR binding potential in the inferofrontal cortex and anterior cingulate regions during placebo, compared to matched controls. Further studies are warranted to examine the relationship of muOR availability with BUP therapeutic actions, and the clinical implications of increased muOR binding during withdrawal.
Subject(s)
Buprenorphine/pharmacology , Heroin Dependence/metabolism , Narcotics/pharmacology , Receptors, Opioid, mu/drug effects , Adult , Analgesics, Opioid , Brain/diagnostic imaging , Brain Chemistry , Double-Blind Method , Fentanyl/analogs & derivatives , Heroin Dependence/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Tomography, Emission-ComputedABSTRACT
The regional cerebral blood flow (rCBF) responses to a combat stress-related auditory stimulus was examined in Vietnam veterans diagnosed with posttraumatic stress disorder (PTSD). Based on prior data in healthy subjects, we hypothesized that the medial prefrontal cortex may be involved in the processing of stress responses. Twelve male veterans diagnosed with PTSD, 11 age-matched, combat-exposed subjects without PTSD, and 12 healthy control subjects were studied with single-photon emission tomography and the blood flow tracer [99mTc]-HMPAO. Subjects were studied twice, while listening to combat sounds or white noise. Significant increases in the blood flow to the medial prefrontal cortex were observed in PTSD patients, but not in the control groups, which correlated at trend levels with psychophysical measures of stress response. These data support the involvement of the medial prefrontal cortex in the pathophysiology of PTSD, possibly mediating some of its symptoms.
Subject(s)
Prefrontal Cortex/diagnostic imaging , Stress Disorders, Post-Traumatic/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Veterans , Acoustic Stimulation , Adult , Affect , Analysis of Variance , Cerebrovascular Circulation , Electromyography , Galvanic Skin Response , Heart Rate , Humans , Male , Middle Aged , Prefrontal Cortex/blood supply , Self Disclosure , Stress Disorders, Post-Traumatic/physiopathology , Stress, Psychological/physiopathology , Technetium Tc 99m Exametazime , United States , VietnamABSTRACT
In a SK-N-BE human neuroblastoma cell line the incubation of rubidium (1 and 10 mM) for 24 h significantly increased IP2 formation, whereas it apparently did not affect other inositol phosphates. In comparison to lithium (10 mM), which significantly enhanced inositolmonophosphate and IP2 accumulation following carbamoylcholine (1 mM) stimulation, rubidium at the same concentration, was unable to affect inositol phosphate accumulation. In conclusion, the present experiments show that rubidium, compared with lithium, shows a different profile on phosphoinositide metabolism since its main action is an increase in phosphatidylinositol turnover. These results may have some relevance to the use of rubidium as antidepressant in man.