Neuropharmacologycal study of the interaction between cannabinoid and opioid circuitsd of the substantia nigra, pars reticulatas, on the activity of the nigrotectal gabaergic pathways, and of the your role in the modulation of the innate fear-induced antinociception

Author(s)

Juliana Almeida da Silva

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2011-05-20

Examining board members

Norberto Cysne Coimbra; Liana Lins Melo; Leonardo Resstel Barbosa Moraes

• Advisor: Norberto Cysne Coimbra

Abstract

There is a great scientific interest in searching the neuropsychopharmacological bases of behavioural reactions associated to fear and panic. Many studies suggest that the mesencephalic tegmentum (MT) a mesencephalic division rich GABA, opiod and endocannabinoid containing neurons and/or receptors complex control on defensive responses during imminent danger conditions. It is also known that the periaquedutal grey matter (PAG), the deep layers of colliculus superior (cpCS) and the colliculus inferior (CI) are important structures related to innate fear and defence as well as to the organization of fear-induced antinociception. In addition neo-striatal-nigrotectal pathways are involved in the modutation of defensive responses elaborated in the dorsal midbrain, the central mesencephalic is rich in endocannabinoids. There are interactions between opioid and GABAergic pathways in these processes. The aim of this work is to study the role of the interaction between opioid anda endocannabinoide-mediated neurotransmission on the activity of GABAergic nigro-collicular pathways. Microinjections of non-selective ande selective agonist and antagonists of opioid an canabinoid receptor were performed in the SNpr before the GABAA receptor blockade in the dorsal midbrain (SCPdl/cpCS). The GABAA receptor blockade in the Mesencephalic tectum elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Microinjection of opioid and cannabinoid agonists in the SNpr increased the fear-induced antinociception and the treatment of the ventral midbrain with antagonists caused opposite effect .These data suggest a clear interaction between opioids and endocannabinoids pathways of the SNpr, in the modulation of the behaviour that has been related to the innate fear and the attacks of panic, being enlisted receiving endocannabinoids of type CB1 and CB2 of mesencephalic tegmentum, to the side of opioids receptors (-opioid receptor antagonist and µ1-opioid receptor antagonist) in the modulation of nigro-tectal GABAergic pathways. (AU)

• FAPESP's process: 09/02458-9 - Neuropharmacological study of the interaction between cannabinoid and opioid circuits of the substantia nigra, pars reticulata, on the activity of the nigrotectal GABAergic pathways, and of its role in the modulation of the innate fear-induced analgesia
• Grantee: Juliana Almeida da Silva
• Support Opportunities: Scholarships in Brazil - Master