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Nat Commun ; 11(1): 306, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949158

RESUMO

With the rise of e-cigarette use, teen nicotine exposure is becoming more widespread. Findings from clinical and preclinical studies show that the adolescent brain is particularly sensitive to nicotine. Animal studies have demonstrated that adolescent nicotine exposure increases reinforcement for cocaine and other drugs. However, the mechanisms that underlie these behaviors are poorly understood. Here, we report reactive microglia are critical regulators of nicotine-induced increases in adolescent cocaine self-administration. Nicotine has dichotomous, age-dependent effects on microglial morphology and immune transcript profiles. A multistep signaling mechanism involving D2 receptors and CX3CL1 mediates nicotine-induced increases in cocaine self-administration and microglial activation. Moreover, nicotine depletes presynaptic markers in a manner that is microglia-, D2- and CX3CL1-dependent. Taken together, we demonstrate that adolescent microglia are uniquely susceptible to perturbations by nicotine, necessary for nicotine-induced increases in cocaine-seeking, and that D2 receptors and CX3CL1 play a mechanistic role in these phenomena.


Assuntos
Cocaína/farmacologia , Comportamento de Procura de Droga/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Nicotina/farmacologia , Aminopiridinas/farmacologia , Animais , Quimiocina CX3CL1/metabolismo , Modelos Animais de Doenças , Sistemas Eletrônicos de Liberação de Nicotina , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Minociclina/farmacologia , Fenótipo , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D2/efeitos dos fármacos , Reforço Psicológico , Recompensa , Autoadministração , Sinaptofisina
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