Effects of the triple monoamine uptake inhibitor amitifadine on pain-related depression of behavior and mesolimbic dopamine release in rats.

ABSTRACT: Pain-related depression of behavior and mood is a key therapeutic target in the treatment of pain. Clinical evidence suggests a role for decreased dopamine (DA) signaling in pain-related depression of behavior and mood. Similarly, in rats, intraperitoneal injection of dilute lactic acid (IP acid) serves as a chemical noxious stimulus to produce analgesic-reversible decreases in both (1) extracellular DA levels in nucleus accumbens (NAc) and (2) intracranial self-stimulation (ICSS), an operant behavior reliant on NAc DA. Intraperitonial acid-induced depression of ICSS is blocked by DA transporter (DAT) inhibitors, but clinical viability of selective DAT inhibitors as analgesics is limited by abuse potential. Drugs that produce combined inhibition of both DA and serotonin transporters may re

SUBMITTER: Miller LL 

PROVIDER: S-EPMC4351716 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature