Ameliorative and exacerbating effects of [pGlu(4),Cyt(6)]AVP((4-9)) on impairment of step-through passive avoidance task performance by group II metabotropic glutamate receptor-related drugs in mice.
To examine the effect of the arginine-vasopressin fragment, [pGlu(4),Cyt(6)]AVP((4-9)) (AVP4-9), on group II metabotropic glutamate receptor (mGluR2/3) agonist and antagonist induced impairment of passive avoidance (PA) task performance, AVP4-9 or phorbol 12-myristate 13-acetate (PMA) was administered in the presence of mGluR2/3-related drugs that induced the impairment of the step-through-type PA task performance. The PA task performance was evaluated in terms of the latency (the time that elapsed prior to entry into the dark compartment) at 24 h after the electrical stimulation. The subcutaneous injection of AVP4-9 at 1 mug/kg had the greatest facilitative effect on the performance, and the facilitative effect of AVP4-9 was inhibited by NPC-15437, a specific protein kinase C (PKC) inhibitor. The injection of AVP4-9 ameliorated PA task performance impairment induced by DCG-IV, an mGluR2/3 agonist. Intracisternal injection of PMA, a PKC activator, also ameliorated the DCG-IV-induced impairment. High doses of AVP4-9 exacerbated the PA task performance impairment induced by LY341495 (an mGluR2/3 antagonist), and PMA injection (1 mug) also exacerbated the impairment induced by the antagonist. These results suggest that an increase in the activity of the PKC-signaling pathway may not always facilitate PA task performance; therefore, AVP4-9 can either enhance or inhibit memory performance in mice.
Sato
Tomoaki
T
Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences. tomsato@dentb.hal.kagoshima-u.ac.jp
Ishida
Takayuki
T
Tanaka
Koh-Ichi
K
Ohnishi
Yoshiko
Y
Irifune
Masahiro
M
Mimura
Tamotsu
T
Nishikawa
Takashige
T
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010880:Piperidines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011930:Reaction Time / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013647:Task Performance and Analysis
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C069701:NPC 15437; D011493:Protein Kinase C