The Blockade of µ1- and κ-Opioid Receptors in the Inferior Colliculus Decreases the Expression of Panic Attack-Like Behaviours Induced by Chemical Stimulation of the Dorsal Midbrain

Abstract

Background: Gamma-aminobutyric acid (GABA)ergic and opioid systems play a crucial role in the neural modulation of innate fear organised by the inferior colliculus (IC). In addition, the IC is rich in GABAergic fibres and opioid neurons, which are also connected to other mesencephalic structures, such as the superior colliculus and the substantia nigra. However, the contribution of distinct opioid receptors (ORs) in the IC during the elaboration and expression of innate fear and panic-like responses is unclear. The purpose of the present work was to investigate a possible integrated action exerted by ORs and the GABA_A receptor-mediated system in the IC on panic-like responses. Methods: The effect of the blockade of either µ₁- or κ-ORs in the IC was evaluated in the unconditioned fear-induced responses elicited by GABA_A antagonism with bicuculline. Microinjections of naloxonazine, a µ₁-OR antagonist, or nor-binaltorphimine (nor-BNI), a κ-OR antagonist, were made into the IC, followed by intramesencephalic administration of the GABA_A-receptor antagonist bicuculline. The defensive behaviours elicited by the treatments in the IC were quantitatively analysed, recording the number of escapes expressed as running (crossing), jumps, and rotations, over a 30-min period in a circular arena. The exploratory behaviour of rearing was also recorded. Results: GABA_A-receptor blockade with bicuculline in the IC increased defensive behaviours. However, pretreatment of the IC with higher doses (5 µg) of naloxonazine or nor-BNI followed by bicuculline resulted in a significant decrease in unconditioned fear-induced responses. Conclusions: These findings suggest a role played by µ₁- and κ-OR-containing connexions and GABA_A receptor-mediated neurotransmission on the organisation of panic attack-related responses elaborated by the IC neurons.