Dopamine-receptor stimulation in the prefrontal cortex ameliorates stress-induced rotarod impairment.
Exposure to chronic stress is thought to play an important role in the etiology of depression. In this disorder, dopaminergic dysfunction in the prefrontal cortex (PFC) is thought to be involved. Indeed, chronic stress reduces dopaminergic transmission in the rat PFC or induces a behaviorally depressive state. However, a relationship between the reduced dopaminergic activity and the behavior of the chronically stressed rats has not been proven. Here, we examined the effects of local application of a dopamine Type I (D(1)) receptor-specific agonist, SKF 81297, in the PFC on the chronic-stress-induced depressive state using a rotarod test. The chronic stress produced by water immersion and restraint for 4 weeks followed by recovery for 10 days impaired the rotarod performance without changing the traction performance or locomotor activity. Although intra-PFC infusion of 1 or 10 ng of SKF 81297 did not affect this impairment, 100 ng of SKF 81297 significantly ameliorated it. These results suggest that the chronic-stress-induced depressive state is caused by a D(1) receptor-mediated hypodopaminergic mechanism in the PFC. These findings will further understanding of the mechanisms underlying the pathophysiology of depression.
Mizoguchi
Kazushige
K
Pharmacology Department, Central Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. mizoguchi_kazushige@mail.tsumura.co.jp
Yuzurihara
Mitsutoshi
M
Nagata
Mitsunobu
M
Ishige
Atsushi
A
Sasaki
Hiroshi
H
Tabira
Takeshi
T
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology / Q000523:psychology
D001552:Benzazepines; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; C067113:SK&F 81297