Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration

GARCIA KELLER, C.; KUPICHNIK, Y.; GIPSON, C.; BROWN, R.; SPENCER, S.; BOLLATI, F.; ESPARZA, M.A.; ROBERTS-WOLFE, D.J.; HEINSBROEK, J.A.; BOBADILLA, A.C.; CANCELA, L.M.; KALIVAS, P.W.

MOLECULAR PSYCHIATRY

NATURE PUBLISHING GROUP

Año: 2015 p. 1 - 7

1359-4184

There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments thelocomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbidstress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine selfadministrationare induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleusaccumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spinemorphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stressproduced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acutestress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in theaccumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration wasabolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However,ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin theincreased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine bynormalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.