Attenuated dopamine receptor signaling in nucleus accumbens core in a rat model of chemically-induced neuropathy.

Neuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Intraplantar formalin injection produces local necrosis over a two-week period and has been used to model neuropathy in rats. To determine whether neuropathy alters dopamine (DA) receptor responsiveness in mesolimbic brain regions, we examined dopamine D₁-like and D₂-like receptor (D_1/2R) signaling and expression in male rats 14 days after bilateral intraplantar formalin injections into both rear paws. D₂R-mediated G-protein activation and expression of the D₂R long, but not short, isoform were reduced in nucleus accumbens (NAc) core, but not in NAc shell, caudate-putamen or ventral tegmental area of formalin- compared to saline-treated rats. In addition, D₁R-stimulated adenylyl cyclase activity was also reduced in NAc core, but not in NAc shell or prefrontal cortex, of formalin-treated rats, whereas D₁R expression was unaffected. Other proteins involved in dopamine neurotransmission, including dopamine uptake transporter and tyrosine hydroxylase, were unaffected by formalin treatment. In behavioral tests, the potency of a D₂R agonist to suppress intracranial self-stimulation (ICSS) was decreased in formalin-treated rats, whereas D₁R agonist effects were not altered. The combination of reduced D₂R expression and signaling in NAc core with reduced suppression of ICSS responding by a D₂R agonist suggest a reduction in D₂ autoreceptor function. Altogether, these results indicate that intraplantar formalin produces attenuation of highly specific DA receptor signaling processes in NAc core of male rats and suggest the development of a neuropathy-induced allostatic state in both pre- and post-synaptic DA receptor function.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}