Blockade of group II metabotropic glutamate receptors produces hyper-locomotion in cocaine pre-exposed rats by interactions with dopamine receptors.
It was previously reported that blockade of group II metabotropic glutamate receptors (mGluRs) produces hyper-locomotion in rats previously exposed to amphetamine, indicating that group II mGluRs are well positioned to modulate the expression of behavioral sensitization by amphetamine. The present study further examined the locomotor activating effects of specific blockade of these receptors after cocaine pre-exposures. First, rats were pre-exposed to seven daily injections of cocaine (15mg/kg, IP). When challenged the next day with an injection of either saline or the group II mGluR antagonist LY341495 (0.5, 1.0 or 2.5mg/kg, IP), they produced hyper-locomotor activity, measured by infrared beam interruptions, to LY341495 compared to saline in a dose-dependent manner. Second, rats were pre-exposed to either saline or seven daily injections of cocaine (15mg/kg, IP). Three weeks later, when they were challenged with an injection of either saline or LY341495 (1.0mg/kg, IP), only rats pre-exposed to cocaine produced hyper-locomotor activity to LY341495 compared to saline. These effects, however, were not present when dopamine D1 (SCH23390; 5 or 10microg/kg), but not D2 (eticlopride; 10 or 50microg/kg), receptor antagonist was pre-injected, indicating that this cocaine-induced hyper-locomotor activity to LY341495 may be mediated in dopamine D1 receptor-dependent manner. These results suggest that group II mGluRs may be adapted to interact with dopaminergic neuronal signaling in mediating the sensitized locomotor activity produced by repeated cocaine pre-exposures.
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.
Jang
Ju Kyong
JK
Kim
Jeong-Hoon
JH
D000596:Amino Acids / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D014966:Xanthenes / Q000009:adverse effects
D000596:Amino Acids; D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D011954:Receptors, Dopamine; D018094:Receptors, Metabotropic Glutamate; D012457:Salicylamides; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D003042:Cocaine; C045989:eticlopride