CB1 CANNABINOID RECEPTOR-MEDIATED ANANDAMIDE SIGNALING MECHANISMS OF THE INFERIOR COLLICULUS MODULATE THE HALOPERIDOL-INDUCED CATALEPSY

Author(s)

Medeiros, P. ; de Freitas, R. L. ; Silva, M. O. ; Coimbra, N. C. ; Melo-Thomas, L.

• Document type: Journal article
• Source: Neuroscience; v. 337, p. 17-26, NOV 19 2016.
• Web of Science Citations: 3

Abstract

The inferior colliculus (IC), a midbrain structure that processes acoustic information of aversive nature, is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Previous evidence relating the IC to motor behavior shows that glutamatergic and GABAergic mechanisms in the IC exert influence on systemic haloperidol-induced catalepsy. There is substantial evidence supporting a role played by the endocannabinoid system as a modulator of the glutamatergic neurotransmission, as well as the dopaminergic activity in the basal nuclei and therefore it may be considered as a potential pharmacological target for the treatment of movement disorders. The present study evaluated if the endocannabinoid system in the IC plays a role in the elaboration of systemic haloperidol-induced catalepsy. Male Wistar rats received intracollicular microinjection of either the endogenous cannabinoid anandamide (AEA) at different concentrations (5, 50 or 100 pmol/0.2 mu l), the CB1 cannabinoid receptor antagonist AM251 at 50, 100 or 200 pmol/0.2 mu l or vehicle, followed by intraperitoneal (IP) administration of either haloperidol at 0.5 or 1 mg/kg or physiological saline. Systemic injection of haloperidol at both doses (0.5 or 1 mg/kg, IP) produced a cataleptic state, compared to vehicle/physiological saline-treated group, lasting 30 and 50 min after systemic administration of the dopaminergic receptors non-selective antagonist. The midbrain microinjection of AEA at 50 pmol/0.2 mu l increased the latency for stepping down from the horizontal bar after systemic administration of haloperidol. Moreover, the intracollicular administration of AEA at 50 pmol/0.2 mu l was able to increase the duration of catalepsy as compared to AEA at 100 pmol/0.2-mu l-treated group. Intracollicular pretreatment with AM251 at the intermediate concentration (100 pmol/0.2 mu l) was able to decrease the duration of catalepsy after systemic administration of haloperidol. However, neither the intracollicular microinjection of AM251 at the lowest (50 pmol/0.2 mu l) nor at the highest (200 pmol/0.2 mu l) concentration was able to block the systemic haloperidol-induced catalepsy. Furthermore, the intracollicular administration of AM251 at 100 pmol/0.2 mu l was able to decrease the duration of catalepsy as compared to AM251 at 50 pmol/0.2 mu l- and AM251 at 200 pmol/0.2-mu l-treated group. The latency for stepping down from the horizontal bar-induced by haloperidol administration-was decreased when microinjection of AEA at 50 pmol/0.2 mu l was preceded with blockade of CB1 receptor with AM251 (100 pmol/0.2 mu l). Our results strengthen the involvement of CB1-signaled endocannabinoid mechanisms of the IC in the neuromodulation of catalepsy induced by systemic administration of the dopaminergic receptors non-selective antagonist haloperidol. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 14/11869-0 - Multi-use equipment approved in grant 2013/12916-0: deep brain stimulation (DBS) (Thomas mini matrix system - Thomas recording GmbH® - Winchester Strasse - Giessen - Germany)
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 11/01409-4 - Electrical stimulation and recording of the neural activity into the inferior colliculus during the haloperidol-induced catalepsy: a behavioral and electrophysiologic study
• Grantee: Liana Melo-Thomas
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/25167-2 - Role of glutamatergic, endocannabinoid and endovaniloid systems of medial pre-frontal cortex in neurophatic pain model: Investigation of panic and chronic pain comorbidity
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/12916-0 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Research Grants - Young Investigators Grants