Effects of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine on phencyclidine-induced behavior and expression of the immediate-early genes in the discrete brain regions of rats.
Because of the possible interaction between adenosine receptors and dopaminergic functions, the compound acting on the specific adenosine receptor subtype may be a candidate for novel antipsychotic drugs. To elucidate the antipsychotic potential of the selective adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA), we examined herein the effects of CPA on phencyclidine (PCP)-induced behavior and expression of the immediate-early genes (IEGs), arc, c-fos and jun B, in the discrete brain regions of rats. PCP (7.5 mg/kg, s.c.) increased locomotor activity and head weaving in rats and this effect was significantly attenuated by pretreatment with CPA (0.5 mg/kg, s.c.). PCP increased the mRNA levels of c-fos and jun B in the medial prefrontal cortex, nucleus accumbens and posterior cingulate cortex, while leaving the striatum and hippocampus unaffected. CPA pretreatment significantly attenuated the PCP-induced increase in c-fos mRNA levels in the medial prefrontal cortex and nucleus accumbens. CPA also significantly attenuated the PCP-induced arc expression in the medial prefrontal cortex and posterior cingulate cortex. When administered alone, CPA decreased the mRNA levels of all IEGs examined in the nucleus accumbens, but not in other brain regions. Based on the ability of CPA to inhibit PCP-induced hyperlocomotion and its interaction with neural systems in the medial prefrontal cortex, posterior cingulate cortex and nucleus accumbens, the present results provide further evidence for a significant antipsychotic effect of the adenosine A(1) receptor agonist.
Gotoh
Leo
L
Department of Chemistry, Faculty of Science, Kyushu University, Ropponmatsu, Fukuoka 810-8560, Japan.
Kawanami
Noriko
N
Nakahara
Tatsuo
T
Hondo
Hisao
H
Motomura
Keisuke
K
Ohta
Eiko
E
Kanchiku
Izumi
I
Kuroki
Toshihide
T
Hirano
Makoto
M
Uchimura
Hideyuki
H
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000235:genetics; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D006213:Hallucinogens / Q000494:pharmacology; D019416:Head Movements / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism
D014150:Antipsychotic Agents; D003598:Cytoskeletal Proteins; D006213:Hallucinogens; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; C092069:activity regulated cytoskeletal-associated protein; C048599:N(6)-cyclopentyladenosine; D010622:Phencyclidine; D000241:Adenosine; D004298:Dopamine