TY - JOUR
T1 - Regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation
AU - Thorpe, Andrew J.
AU - Mullett, Mary A.
AU - Wang, ChuanFeng
AU - Kotz, Catherine M
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Orexin A (OX-A) administered in the lateral hypothalamus (LH) increases feeding in a dose-dependent manner. The LH is a relatively large neural structure with a heterogeneous profile of neural inputs, efferent projections, and orexin receptor distribution. We sought to determine the LH region most sensitive to the feeding stimulatory effect of OX-A injection. Fifty-six male Sprague-Dawley rats were fitted with cannulas 1 mm above four separate LH regions ∼1 mm apart in the rostral-caudal direction. There were 14-16 animals/LH region. After recovery, animals received either artificial cerebrospinal fluid or OX-A (250, 500, or 1,000 pmol). To determine whether there is a circadian effect of LH OX-A on the feeding response, we performed injections at 0200, 0900, 1400, and 2100. Food intake was measured at 1, 2, and 4 h after injection. The most rostral extent of the LH was the only region in which injection of OX-A significantly stimulated feeding. Within this region, feeding was increased at all times of the day, although the most robust and only significant feeding response occurred after the afternoon injection (1400) of OX-A. To determine the extent to which the metabolic status of the rat contributed to the circadian specificity of orexin-induced feeding, animals were placed on a restricted diet and injected with OX-A in the most rostral region of the LH. Under these conditions, OX-A significantly increased feeding and more robustly when compared with animals on a nonrestricted diet. These data suggest that the rostral LH is the only region of the LH sensitive to the injection of OX-A, and the metabolic status of the animal at the time of injection may influence the feeding response to OX-A.
AB - Orexin A (OX-A) administered in the lateral hypothalamus (LH) increases feeding in a dose-dependent manner. The LH is a relatively large neural structure with a heterogeneous profile of neural inputs, efferent projections, and orexin receptor distribution. We sought to determine the LH region most sensitive to the feeding stimulatory effect of OX-A injection. Fifty-six male Sprague-Dawley rats were fitted with cannulas 1 mm above four separate LH regions ∼1 mm apart in the rostral-caudal direction. There were 14-16 animals/LH region. After recovery, animals received either artificial cerebrospinal fluid or OX-A (250, 500, or 1,000 pmol). To determine whether there is a circadian effect of LH OX-A on the feeding response, we performed injections at 0200, 0900, 1400, and 2100. Food intake was measured at 1, 2, and 4 h after injection. The most rostral extent of the LH was the only region in which injection of OX-A significantly stimulated feeding. Within this region, feeding was increased at all times of the day, although the most robust and only significant feeding response occurred after the afternoon injection (1400) of OX-A. To determine the extent to which the metabolic status of the rat contributed to the circadian specificity of orexin-induced feeding, animals were placed on a restricted diet and injected with OX-A in the most rostral region of the LH. Under these conditions, OX-A significantly increased feeding and more robustly when compared with animals on a nonrestricted diet. These data suggest that the rostral LH is the only region of the LH sensitive to the injection of OX-A, and the metabolic status of the animal at the time of injection may influence the feeding response to OX-A.
KW - Hypocretin
KW - Hypothalamus
KW - Melanin-concentrating hormone
KW - Restricted diet
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U2 - 10.1152/ajpregu.00344.2002
DO - 10.1152/ajpregu.00344.2002
M3 - Article
C2 - 12736178
AN - SCOPUS:0038176915
SN - 0363-6119
VL - 284
SP - R1409-R1417
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 6 53-6
ER -