Glutamatergic Mechanisms of Comorbidity Between Acute Stress and Cocaine Self-administration

GARCIA KELLER C; KUPCHIK Y; GIPSON C; BROWN RM; SPENCER S; BOLLATI F; ESPARZA MA; ROBERTS-WOLFE D; HEINSBROEK J; CANCELA LM; KALIVAS PW

MOLECULAR PSYCHIATRY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2016

1359-4184

here is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens cor