Journal Article

An altered spinal serotonergic system contributes to increased thermal nociception in an animal model of depression

Rojo, María Luisa, Díaz, Álvaro, Rodríguez-Gaztelumendi, Antonio, Pazos, Ángel

2014

Overview

The olfactory bulbectomized (OB) rat, an animal model of chronic depression with comorbid anxiety, exhibits a profound dysregulation of the brain serotonergic signalling, a neurotransmission system involved in pain transmission and modulation. We here report an increased nociceptive response of OB rats in the tail flick test which is reverted after chronic, but not acute, administration of fluoxetine. Autoradiographic studies demonstrated down-regulation of 5-HT transporters ([ 3 H]citalopram binding) and decreased functionality of 5-HT 1A receptors (8-OH-DPAT-stimulated [ 35 S]GTPγS binding) in the dorsal horn of the lumbar spinal cord in OB rats. Acute administration of fluoxetine (5–40 mg/kg i.p.) did not modify tail flick latencies in OB rats. However, chronic fluoxetine (10 mg/kg/day s.c., 14 days; osmotic minipumps) progressively attenuated OB-associated thermal hyperalgesia, and a total normalization of the nociceptive response was achieved at the end of the treatment with the antidepressant. In these animals, autoradiographic studies revealed further down-regulation of 5-HT transporters and normalization in the functionality of 5-HT 1A receptors on the spinal cord. On the other hand, acute morphine (0.5–10 mg/kg s.c.) produced a similar analgesic effect in OB and sham and OB rats, and no changes were detected in the density ([ 3 H]DAMGO binding) and functionality (DAMGO-stimulated [ 35 S]GTPγS binding) of spinal μ-opioid receptors in OB rats before and after chronic fluoxetine. Our findings demonstrate the participation of the spinal serotonergic system in the increased thermal nociception exhibited by the OB rat and the antinociceptive effect of chronic fluoxetine in this animal model of depression.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Analgesics / Analysis / Animals / Antidepressants / Antidepressive Agents - therapeutic use / Anxiety / Autoradiography / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Brain / Chronic pain / Citalopram / Comorbidity / Depression - complications / Depression - drug therapy / Depression - pathology / Depression, Mental / Disease Models, Animal / Drug therapy / Enkephalin, Ala-MePhe-Gly- - pharmacokinetics / Exploratory Behavior - physiology / Fluoxetine / Fundamental and applied biological sciences. Psychology / Genetic aspects / Guanosine 5'-O-(3-Thiotriphosphate) - pharmacokinetics / Hyperalgesia / Hyperalgesia - drug therapy / Hyperalgesia - etiology / Male / Management / Mental depression / Morphine / Morphine - therapeutic use / Narcotics / Neurology / Neurosciences / Neurotransmitter Agents - pharmacokinetics / Nociception / Normalization / Olfactory Bulb - injuries / Olfactory Bulb - surgery / Opioids / Pain / Pain Measurement / Physiological aspects / Radiography / Radioisotopes - pharmacokinetics / Rats / Rats, Sprague-Dawley / Receptor, Serotonin, 5-HT1A - metabolism / Receptors, Opioid, mu - metabolism / Regulation / Research Article / Risk factors / Serotonin - metabolism / Serotonin Agents - pharmacokinetics / Serotonin Plasma Membrane Transport Proteins - metabolism / Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors / Spinal cord / Spinal Cord - diagnostic imaging / Spinal Cord - drug effects / Spinal Cord - metabolism / Vertebrates: nervous system and sense organs