Acute exercise inhibits gastric emptying of liquids in rats: influence of the NO-cGMP pathway

We previously found that acute exercise inhibited the gastric emptying of liquid in awake rats by causing an acid-base imbalance. In the present study, we investigated the involvement of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, vasoactive intestinal peptide (VIP), and corticotropin-releasing factor (CRF) peptide in this phenomenon. Male rats were divided into exercise or sedentary group and were subjected to a 15-min swim session against a load (2.5 or 5% b.w.). The rate of gastric emptying was evaluated after 5, 10, or 20 min postprandially. Separate groups of rats were treated with vehicle (0.9% NaCl, 0.1 mL/100 g, ip) or one of the following agents: atropine (1.0 mg/kg, ip), the NO non-selective inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10.0 mg/kg, ip), or the selective cGMP inhibitor 1H-(1,2,4)oxadiazole[4,3-a]quinoxalin-1-one (ODQ; 5.0 mg/kg, ip), the i-NOS non-specific inhibitor (aminoguanidine; 10.0 mg/kg, ip), the corticotropin-releasing factor receptor antagonist (astressin; 100 µg/kg, ip), or the vasoactive intestinal peptide (VIP) receptor antagonist Lys1, Pro2,5, Arg3,4, Tyr6 (100 µg/kg, ip). Compared to sedentary rats, both the 2.5 and 5% exercise groups exhibited higher (P<0.05) values of blood lactate and fractional gastric dye recovery. Corticosterone and NO levels increased (P<0.05) in the 5% exercised rats. Pretreatment with astressin, VIP antagonist, atropine, L-NAME, and ODQ prevented the increase in gastric retention caused by exercise in rats. Acute exercise increased gastric retention, a phenomenon that appears to be mediated by the NO-cGMP pathway, CRF, and VIP receptors.

Thyrotropin releasing hormone injected into the nucleus accumbens septi selectively increases face grooming in rats

The effect of unilateral injection of peptides into the nucleus accumbens septi (NAS) on subcategories of grooming behavior was studied in male rats. The peptides used were: thyrotropin releasing hormone (TRH), luteinizing hormone releasing hormone (LHRH) and corticotropin releasing hormone (CRH). Male rats (Holtzman strain, 240-270 g body weight) injected with progressive doses of TRH (100, 200 and 400 ng) at 5-day intervals were compared with the control state (injection of artificial cerebrospinal fluid CSF). A selective increase in face grooming was observed with the 100 ng (49.78 + 6.11, N = 18) and 200 ng (50.29 + 7.72, N = 17) doses of TRH (P<0.05 vs CSF injection 26.94 + 3.64, N = 18). Face grooming increased further with the 400 ng dose (55.19 + 8.26, N = 16, P<0.01), but a dose-response curve could not be obtained at the dose range used. Flank scratching, head, body and genital grooming were not altered by the TRH injection, but the rearing behavior was inhibited (10.33 + 1.56; N = 18; 10.76 + 1.77, N = 17; 12 + 2.06, N = 16) (P<0.05 for all doses vs controls, 20.61 + 2.81, N = 18). The rats that received LHRH (75 ng, N = 16) and CRH (100 ng, N = 14) did not show behavioral changes when compared with their control states. The results show that injection on TRH into the NAS, but not the injection of LHRH or CRH, selectively increases face grooming without affecting other subcategories of grooming at the doses used, and appears to link this peptide with the neural substrate of stereotyped behavior.

Distinct grooming patterns induced by intracerebroventricular injection of CRH, TRH and LHRH in male rats

This paper reports the effects on grooming, related behaviors and levels of anxiety induced by the hypophysiotropic peptides corticotropin-releasing hormone (CRH, 1 mug, 0.2 nmol, icv), thyrotropin-releasing hormone (TRH, 100 mug, 275 nmol, icv) and luteinizing hormone-releasing hormone (LHRH, 1.5 mug, 1.3 nmol, icv) administered into the lateral ventricle of the brain (icv) of adult male rats of a Holtzman-derived colony (N = 15, each group). CRH induced an increase in total grooming scores, whereas LHRH, TRH and vehicle had no effect. CRH strongly increased face and head grooming and induced head shakes. The time spent in rearing and gnawing was significantly decreased. In the plus-maze, CRH reduced the time of exploration in the open arm. TRH increased face grooming and induced body shakes. LHRH had no effect on grooming or rearing behavior. No body or head shakes were observed after LHRH administration. Scoring of individual grooming elements demonstrated differences in action of the three peptides. Although both CRH and TRH increased face grooming, only CRH induced head grooming. Furthermore, CRH induced predominantly head shakes while TRH increased body shake activity. In contrast, CRH was anxiogenic and TRH appeared to induce stereotyped behavior. From the characterization of grooming elements and related responses, we conclude that each hypophysiotropic peptide induces a specific behavioral pattern.

O valor do teste de estímulo com o hormônio liberador da corticotrofina ovino (oCRH) no diagnóstico diferencial da síndrome de Cushing / The value of the stimulus test with ovine corticotropin-releasing hormone (oCRH) in the differential diagnosis of the Cushing syndrome

A caracterizaçao do CRH ovino (oCRH) trouxe novas perspectivas para o diagnóstico diferencial da síndrome de Cushing (SC). Aplicamos o teste de estímulo com oCRH (l mug/kg peso, IV em bolo) para estudo da reserva hipofisária (ACTH) e adrenal (cortisol) em 17 indivíduos controles normais (CN) e 32 pacientes com SC (doença de Cushing [DC] n=24; adenoma adrenocortical [AA] n=6 e secreçao ectópica de ACTH [SE] n=2). Os CN elevaram significantemente seus níveis de ACTH (basal: 28,9 + 12,7; pico: 59,3.ñ 17,6 pg/ml; média ñ DP) e de cortisol (basal: 10, 1.ñ3,4; pico: 18,3 ñ 5,1 mul/dí) após o oCRH. Os pacientes com DC apresentaram níveis basais mais elevados de ACTH (61,7.ñ 58,2 pg/ml) e de cortisol (22,2 ñ 12,5 mug/dl), que se elevaram significantemente após o oCRH (l8l,3 + l32,9 pg/ml e 37,9 + l7,5 mug/dl, respectivamente). Os pacientes com AA apresentaram níveis de ACTH basais (7,4 ñ 3,1 pg/ml) e no pico da resposta (l6,O ñ l3,1 pg/ml) menores que os dos CN e DC. Os níveis basais de cortisol (l9,6 + 6,9 mug/dl) foram maiores que os dos CN, mas nao mudaram após o oCRH (l9,8 ñ 5,7 mug/dl). Os dois pacientes com SE mostraram níveis basais altos de ACTH (307,7 e 102,8 pg/ml) que se elevaram (para 582,4 e 785,4 pg/ml) com o oCRH. Em um o cortisol aumentou de 17,7 para 30,2 mug/dl, mas no outro nao houve mudança (de 6,3 para 6,2 mug/dl). A resposta ao teste foi considerada positiva quando o pico de ACTH foi > 37,7 pg/ml e /ou o incremento de cortisol foi > 2O por cento, o que aconteceu nos CN, DC e (excepcionalmente) em um paciente com SE. A resposta do cortisol ao oCRH mostrou sensibilidade de 100 por cento e especificidade de 87,5 por cento na discriminaçao entre SC hipofisária e extra-hipofisária, em comparaçao com os 75 por cento conseguidos com a supressao pela dexametasona em doses elevadas (8 ou 16 mg em dose única). A eficácia diagnostica é aumentada com a associaçao dos dois testes. Assim, o teste de estímulo com oCRH é útil e prático na determinaçao do diagnóstico diferencial da SC.