Effect of the antidepressant nefazodone on the density of cells expressing mu-opioid receptors in discrete brain areas processing sensory and affective dimensions of pain.
BACKGROUND
The principal use of antidepressants is in the treatment of depression and affective disorders. Antidepressants have also been used as an adjuvant to analgesics in pain treatment. However, in chronic treatment, their antinociceptive and antidepressive effects coexist simultaneously. Antidepressants can interact with the opioid system, which is also involved in regulating nociceptive processing and affective state. Chronic antidepressants could act by increasing mu-opioid receptor expression in many brain areas involved in the regulation of nociception and affective state.


OBJECTIVE
The aim of this study was to evaluate the antinociceptive and antidepressant-like effects and the possible variations in mu-opioid receptor expression induced by a chronic nefazodone treatment in brain areas related to pain and affective state.


METHODS
Wistar rats were chronically treated with nefazodone (10 and 25 mg/kg IP, twice a day, for 14 days). Twelve hours after the last day 14 dose of nefazodone, a tail-flick test was performed. After the administration of a daily dose of nefazodone, Porsolt's test was carried out 12 h after last dose. Two hours after completion of 14 days treatment, other animals were processed for mu-opioid receptor immunocytochemistry using polyclonal antisera raised in rabbits. Several brain regions were analyzed: the frontal and cingulate cortex, the dorsal raphe nucleus and the periaqueductal gray.


RESULTS
Chronic nefazodone treatment induced a significant increase in tail-flick latency and a significant decrease in immobility time at total doses of 20 and 50 mg/kg per day ( P<0.05). In treated animals, the density of neural cells immunostained for mu-opioid receptor in the frontal and cingulate cortices, dorsal raphe nucleus and periaqueductal gray had increased after chronic nefazodone compared to controls.


CONCLUSIONS
Therefore, chronic nefazodone induces antinociceptive and antidepressant-like effects in rats and increases mu-opioid receptor expression in brain areas related to pain and affective state. These results suggest that antidepressants could be effective on somatic and affective dimensions of pain and this action could be related to its influence on the opioid system.
Ortega-Alvaro
Antonio
A
Pharmacology and Neuroscience Research Group (CTS-510), Department of Neuroscience (Pharmacology and Psychiatry), Faculty of Medicine, University of Cadiz, Plaza Fragela 9, 11003 Cádiz, Spain.
Acebes
Ignacio
I
Saracíbar
Gonzalo
G
Echevarría
Enrique
E
Casis
Luis
L
Micó
Juan Antonio
JA
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002452:Cell Count; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004644:Emotions / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D010146:Pain / Q000523:psychology*; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects; D010879:Piperazines; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D012677:Sensation / Q000502:physiology*; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects; D013550:Swimming / Q000523:psychology; D014230:Triazoles / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D017450:Receptors, Opioid, mu; D014230:Triazoles; C051752:nefazodone