Pharmacological Studies of Alcohol Susceptibility and Brain Monoamine Function in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) and Stroke-Resistant Spontaneously Hypertensive Rats (SHRSR)

Pharmacological Studies of Alcohol Susceptibility and Brain
Monoamine Function in Stroke-Prone Spontaneously
Hypertensive Rats (SHRSP) and Stroke-Resistant
Spontaneously Hypertensive Rats (SHRSR)

KANJI YOSHIMOTO, SETSUO KOMURA, HIROYUKI HATTORI,¹ YUKIO YAMORI,¹
AYAKO MIURA,¹ TOSHIHIDE YOSHIDA,² CHIZUKO HIOKI,² BAKU KATO,³
FUMIHIKO FUKUDA,³ SHIHO TANAKA, AYAKO HIRAI, AKIRA NISHIMURA,⁴
YASUKO SAWAI⁴ and MASAHIRO YASUHARA

Department of Legal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, ¹WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases, Kyoto 606-8501, ²First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, ³Department of Health Promoting Acupuncture and Moxibution, Meiji University of Oriental Medicine, Kyoto 629-0392, and ⁴Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto 602-8566

Differences of alcohol drinking behavior, brain dopamine (DA) and serotonin (5-HT) levels and releases in the striatum were investigated in stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched stroke-resistant spontaneously hypertensive rats (SHRSR). Voluntary alcohol (EtOH) consumption in SHRSP rats increased at 1 and 2 hours in the 4 hour time access. In the DA level, SHRSP showed decreases in the caudate-putamen (C/P) and dorsal raphe nucleus (DRN) compared with in SHRSR. 5-HT levels in the C/P, ventral tegmental area-subtantia nigra (V/S) and DRN of the SHRSP were decreased compared with that in SHRSR. The basal extracellular levels of 5-HT release in the C/P were increased in SHRSP as compared with those in SHRSR. K⁺- or EtOH-induced DA and 5-HT releases in the C/P of the SHRSP were a lower magnitude than those in SHRSR. Increased basal extracellular 5-HT releases showing low levels of 5-HT in the C/P of SHRSP mean an abnormality of serotonergic neuronal functions in a normal physiological condition. Higher voluntary alcohol drinking behavior, so called lower susceptibility to EtOH, in the SHRSP may be associated with the degenerated rewarding system including the DRN. These results suggest that the hypertensive state causes the dysfunction in the striatum of the brain rewarding system and induces the risk for increasing alcohol consumption to compensate for the alteration of serotonergic neurons.

keywords —— alcohol; brain monoamines; SHR rats

===============================

Tohoku J. Exp. Med., 2003, 201, 11-22

Address for reprints: Kanji Yoshimoto, Ph.D., Department of Legal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi, Kamigyo-ku, Kyoto 602-8566 Japan.

e-mail: kyoshimo@basic.kpu-m.ac.jp