CART peptide and opioid addiction: Expression changes in male rat brain

• Single high-dose of morphine elevates CART mRNA and protein in NAc, PFC and striatum.
• Morphine withdrawal up-regulates CART mRNA and protein in NAc, PFC and striatum.
• Chronic morphine abuse down-regulates CART mRNA and protein in NAc and striatum.
• Long-term abstinence can reverse some changes in CART expression in the reward pathway.

Previous studies have shown the prominence of cocaine- and amphetamine-regulated transcript (CART) peptide in rewarding and reinforcing effects of drugs of abuse specially psychostimulants. The data regarding the effects of different stages of opioid addiction on CART expression and the interconnection between CART and opioids are not much available. Here we have studied the changes in the expression level of CART mRNA and protein in various parts of the brain reward pathway in different stages of opioid addiction. Groups of male rats received acute low-dose (10 mg/kg), acute high-dose (80 mg/kg) and chronic escalating doses of morphine. In addition, withdrawal and abstinence states were evaluated after injection of naloxone (1 mg/kg) and long-term maintenance of addicted animals, respectively. Expression of CART mRNA in the brain was measured by real-time PCR method. Western blotting was used to quantify the protein level. CART mRNA and protein were both up-regulated in high-dose morphine-administered animals and also in the withdrawal group in the nucleus accumbens (NAc), striatum and prefrontal cortex (PFC). In the addicted group, CART mRNA and protein were both down-regulated in NAc and striatum. In the abstinent group, CART mRNA was down-regulated in NAc. In the hippocampus, the only observed change was the up-regulation of CART mRNA in the withdrawal group. We suggest that the modulatory role of CART peptide in rewarding and reinforcing effects of opioids weakens when opioids are used for a long time and is stimulated when acute stress such as naloxone-induced withdrawal syndrome or acute high-dose administration of morphine occurs to the animal.