Effects of Repeated Treatment with Monoamine-transporter-inhibitor Antidepressants on Pain-related Depression of Intracranial Self-stimulation in Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2020 May 9

PMID 32382785

Citations 9

Authors

L P Legakis

L Karim-Nejad

S S Negus

Affiliations

Soon will be listed here.

Abstract

Rationale: Synaptic neurotransmission with dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is terminated primarily by reuptake into presynaptic terminals via the DA, NE, and 5-HT transporters (DAT/NET/SERT, respectively). Monoamine transporter inhibitors constitute one class of drugs used to treat both depression and pain, and therapeutic effects by these compounds often require repeated treatment for days or weeks.

Objectives: The present study compared antinociceptive effects produced by repeated treatment with monoamine transporter inhibitors in a preclinical assay of pain-related depression of positively reinforced operant responding.

Methods: Adult Sprague-Dawley rats equipped with microelectrodes targeting a brain-reward area responded for pulses of electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. Intraperitoneal injection of dilute lactic acid served as a noxious stimulus that repeatedly depressed ICSS and also produced weight loss during 7 days of repeated acid administration.

Results: Acid-induced depression of both ICSS and body weight were completely blocked by repeated pretreatment with the nonsteroidal anti-inflammatory drug ketorolac. The DAT-selective inhibitor bupropion also fully blocked acid-induced ICSS depression and weight loss throughout all 7 days of treatment. The NET-selective inhibitor nortriptyline and the SERT-selective inhibitor citalopram were generally less effective, but both drugs blocked acid-induced ICSS depression by the end of the 7-day treatment. Acid-induced depression of ICSS and body weight were not blocked by the kappa opioid receptor (KOR) agonist U69593 or the KOR antagonist norbinaltorphimine.

Conclusions: These results support effectiveness of bupropion to alleviate signs of pain-related behavioral depression in rats and further suggest that nortriptyline and citalopram produce significant but less reliable effects.

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