RESUMO
Tobacco smoking is highly comorbid with heavy alcohol drinking, yet the interaction of tobacco smoking and alcohol drinking on brain catecholaminergic synaptic markers is unexplored. Here we evaluate the effects of alcohol drinking alone from comorbid alcohol drinking and tobacco smoking on dopamine (DA) and serotonin (5-HT) transporter availability. A total of 14 heavy alcohol drinking smokers (n=6) and nonsmokers (n=8) and 14 age-matched control smokers (n=6) and nonsmokers (n=8) were imaged with [(123)]beta-CIT single photon emission computed tomography. Alcohol drinking smokers and nonsmokers consumed 134.3+/-100.3 and 196.5+/-139.9 drinks, respectively, over the previous month and were imaged during acute withdrawal, eg within 5 days of their last drink. Striatal DA transporter availability was significantly higher (16%, P=0.04) in alcohol drinkers compared to controls. 5-HT transporter availability was also significantly higher in alcohol drinkers vs controls in the brainstem (25%, P=0.001) and the diencephalon (8%, P=0.01). This elevation was restricted to alcohol drinking nonsmokers with higher DA transporter availability in the striatum (26%, P=0.006), and higher 5-HT transporter availability in the diencephalon (26%, P=0.04) and brainstem (42%, P<0.0002). There was a significant positive correlation between days since last drink and 5-HT transporter availability in the diencephalon (r=0.60, P=0.023) and brainstem (r=0.54, P=0.047), in the total group of alcohol drinkers and in the nonsmokers, but not the smokers. During the first week of abstinence, DA and 5-HT transporter availability is higher in alcohol drinking nonsmokers but not in alcohol drinking smokers. Smoking appears to suppress neuroadaptive changes in DA and 5-HT transporters during acute withdrawal from alcohol.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Fumar/metabolismo , Síndrome de Abstinência a Substâncias/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Estudos de Casos e Controles , Cocaína/análogos & derivados , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Compostos Radiofarmacêuticos , Fumar/patologia , Estatística como Assunto , Síndrome de Abstinência a Substâncias/patologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto JovemRESUMO
Human postmortem studies have reported decreases with age in high affinity nicotine binding in brain. We investigated the effect of age on beta(2)-containing nicotinic acetylcholine receptor (beta(2)-nAChR) availability in eight brain regions of living human subjects using the ligand [(123)I]5-IA-85380 ([(123)I]5-IA) and single photon emission computed tomography (SPECT). Healthy, nonsmokers (N=47) ranging in age from 18 to 85 were administered [(123)I]5-IA using a bolus plus constant infusion paradigm and imaged 6-8h later under equilibrium conditions. The effect of age on regional beta(2)-nAChR availability (V(T), regional brain activity/free plasma parent, a measure proportional to the binding potential) was analyzed using linear regression and Pearson's correlation (r). Age and regional beta(2)-nAChR availability were inversely correlated in seven of the eight brain regions analyzed, with decline ranging from 32% (thalamus) to 18% (occipital cortex) over the adult lifespan, or up to 5% per decade. These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of beta(2)-nAChRs in cognitive aging.
Assuntos
Envelhecimento/metabolismo , Química Encefálica/fisiologia , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Regulação para Baixo/fisiologia , Receptores Nicotínicos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azetidinas , Encéfalo/anatomia & histologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Radioisótopos do Iodo , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Piridinas , Receptores Nicotínicos/análise , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto JovemRESUMO
Human postmortem studies have reported decreases with age in high-affinity nicotine binding in brain. We have been investigating in vivo the availability of the beta(2)-containing nicotinic acetylcholine receptor (beta(2)-nAChR) in healthy nonsmokers (18-85 years of age) using [(123)I]5-IA-85380 SPECT imaging. Age and regional beta(2)-nAChR availability (V(T)(,)) have been observed to be inversely correlated in all brain regions analyzed, with decline ranging from 21% (cerebellum) to 36% (thalamus), or by up to 5% per decade of life. Preliminary results have confirmed postmortem reports of age-related decline in high-affinity nicotine binding with age and may elucidate the role of beta(2)-nAChRs in the cognitive decline associated with aging.
