Microinjection of CART peptide 55-102 into the nucleus accumbens blocks both the expression of behavioral sensitization and ERK phosphorylation by cocaine.
The role of the biologically active CART 55-102 peptide in the nucleus accumbens (NAcc) in the expression of cocaine-induced behavioral sensitization was investigated. Rats were divided into four groups: one for saline and the other three for cocaine pre-exposures (15 mg/kg, i.p., once daily for 7 days). After 3 weeks of withdrawal, rats were microinjected into the NAcc either saline or CART 55-102 (1.0, or 2.5 microg/0.5 microl/side) followed by cocaine challenge (10 mg/kg, i.p.). Microinjection into the NAcc of CART 55-102 peptide dose-dependently blocked the expression of locomotor sensitization produced by repeated cocaine pre-exposures. Next, we further examined the effect of CART 55-102 microinjection on extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation levels in the NAcc. Additional four groups of rats were all cocaine pre-exposed and, after 3 weeks of withdrawal, they were either saline or cocaine challenged systemically following microinjection into the NAcc of either saline, CART 55-102 (2.5 microg/0.5 microl/side), or the equivalent mole amount of inactive CART 1-27 peptide. The increase of ERK1/2 phosphorylation levels in the NAcc by cocaine was completely blocked by CART 55-102 microinjection in this site, while it remains unaffected by inactive CART 1-27 peptide. These results suggest that CART 55-102 peptide in the NAcc may play a compensatory inhibitory role in the expression of behavioral sensitization by cocaine and these effects may be mediated by its inhibition of ERK1/2 phosphorylation in this site.
Yoon
Hyung Shin
HS
Department of Physiology, Brain Korea 21 Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, 134 Shinchondong, Seodaemungu, Seoul 120-752, South Korea.
Kim
Seungwoo
S
Park
Hye Kyung
HK
Kim
Jeong-Hoon
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D008845:Microinjections / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein