Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors

Author(s)

Gomes, Felipe V. ; Reis, Daniel G. ; Alves, Fernando H. F. ; Correa, Fernando M. A. ; Guimaraes, Francisco S. ; Resstel, Leonardo B. M.

• Document type: Journal article
• Source: JOURNAL OF PSYCHOPHARMACOLOGY; v. 26, n. 1, p. 10-pg., 2012-01-01.

Abstract

Systemic administration of cannabidiol (CBD) attenuates cardiovascular and behavioral changes induced by re-exposure to a context that had been previously paired with footshocks. Previous results from our group using cFos immunohistochemistry suggested that the bed nucleus of the stria terminalis (BNST) is involved in this effect. The mechanisms of CBD effects are still poorly understood, but could involve 5-HT1A receptor activation. Thus, the present work investigated if CBD administration into the BNST would attenuate the expression of contextual fear conditioning and if this effect would involve the activation of 5-HT1A receptors. Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (six footshocks, 1.5 mA/3 s). Twenty-four hours later freezing and cardiovascular responses (mean arterial pressure and heart rate) to the conditioning box were measured for 10 min. CBD (15, 30 or 60 nmol) or vehicle was administered 10 min before the re-exposure to the aversive context. The second experiment was similar to the first one except that animals received microinjections of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol) 5 min before CBD (30 nmol) treatment. The results showed that CBD (30 and 60 nmol) treatment significantly reduced the freezing and attenuated the cardiovascular responses induced by re-exposure to the aversive context. Moreover, WAY100635 by itself did not change the cardiovascular and behavioral response to context, but blocked the CBD effects. These results suggest that CBD can act in the BNST to attenuate aversive conditioning responses and this effect seems to involve 5-HT1A receptor-mediated neurotransmission. (AU)

• FAPESP's process: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/03187-9 - Involvement of rats medial prefrontal cortex on the aversive response observed in Vogel conflict test: a possible NMDA receptors, nitric oxide and endocannabinoid system pathway
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants