Long-term loss of dopamine release mediated by CRF-1 receptors in the rat lateral septum after repeated cocaine administration. (2013)

Behav Brain Res. 2013 May 16. pii: S0166-4328(13)00283-0. doi: 10.1016/j.bbr.2013.05.012. [Epub ahead of print]

Sotomayor-Zárate R, Renard GM, Araya KA, Carreño P, Fuentealba JA, Andrés ME, Gysling K.


Millennium Science Nucleus in Stress and Addiction, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile; Centro de Neurobiología y Plasticidad Cerebral, Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso.


The lateral septum (LS) is a brain nucleus associated to stress and drug addiction. Here we show that dopamine extracellular levels in the lateral septum are under the control of corticotrophin releasing factor (CRF). Reverse dialysis of 1μM stressin-1, a type 1 CRF receptor (CRF-R1) agonist, induced a significant increase of LS dopamine extracellular levels in saline-treated rats that was blocked by the co-perfusion of stressin-1 with CP-154526, a specific CRF-R1 antagonist. Repeated cocaine administration (15mg/kg; twice daily for 14 days) suppressed the increase in LS dopamine extracellular levels induced by CRF-R1 activation. This suppression was observed 24hours, as well as 21 days after withdrawal from repeated cocaine administration.

In addition, depolarization-induced dopamine release in the LS was significantly higher in cocaine- compared to saline-treated rats. Thus, our results show that the activation of CRF-R1 in the LS induces a significant increase in dopamine extracellular levels. Interestingly, repeated cocaine administration induces a long-term suppression of the CRF-R1 mediated dopamine release and a transient increase in dopamine releasability in the LS.