Neil E. Rowland

Stress induced eating

The relationship of oral behaviors to stress has long been recognized both in humans and in wild animals. In the last decade numerous advances have been made in our understanding of stress-induced feeding predominately because of the development of the simple tail-pinch model of stress induced feeding in rats. Present evidence strongly implicates monoamines and the endogenous opioid peptides as well as other neuropeptides as playing a role in the central regulation of stress-induced eating.

Localization of changes in immediate early genes in brain in relation to hydromineral balance: intravenous angiotensin II

Immediate early genes, detected by Fos- and Jun-like immunoreactivity (FLI, JLI), were induced in discrete regions of the rat brain by intravenous infusion of angiotensin II (Ang II) at dipsogenic doses. The regions included subfornical organ (SFO), organum vasculosum laminae terminalis (OVLT), median preoptic nucleus (MnPO), supraoptic nucleus (SON), and the magnocellular part of the paraventricular hypothalamus (PVH). These responses were sustained for up to 6 h of infusion. In SFO, FLI was induced preferentially in the posterior part, while JLI occurred in more central regions. Cerebroventricular (ICV) injection of the Ang II type 1 receptor (AT-1) antagonist, losartan potassium, completely prevented the FLI induced by Ang II in these brain regions. ICV injection of the Ang II type 2 receptor (AT-2) antagonist, PD 123319, did not reduce Ang II-induced FLI in SFO, OVLT and MnPO, but markedly attenuated the activation in SON and PVH. To determine whether SFO is the primary site for transduction of the circulating Ang II signal, electrolytic lesions were made in or rostral to the SFO. Rats with complete lesions showed a complete absence of Ang-induced FLI in SON and PVH. The data are discussed in terms of functional mapping of the brain regions activated by circulating Ang II and neural circuitry for water intake, including the possible role of AT-2 receptors in PVH and SON.

Autism and Schizophrenia: Intestinal Disorders

We examined Dohans hypothesis that schizophrenia is associated with the absorption of “exorphins” contained in gluten and casein. In addition, because of the work of Reichelt et al. (Reichelt, K.L., Saelid, G., Lindback, J. and Orbeck, H. (1986) Biological Psychiatry 21:1279–1290) and Rodriguez et al. (Rodriguez, Trav, A.L., Barreiro Marin, R, Galvez, Borrero, I.M., del Olmo Romero-Nieva, F. and Diaz Alvarez, A. (1994) Journal of Nervous and Mental Disease Aug; 182(8): 478–479), we carried out similar studies on a group of children with autism. In both syndromes we found similar patterns of peptide containing peaks (Ninhydrin positive) after molecular screening with Sephadex G-15. Immunoglobulin assay of IgA and IgG against gliadin and casein in serum was done. High titer IgG antibodies to gliadin were found in 87% of autistic and 86% of schizophrenic patients and high titer IgG antibodies to bovine casein were found in 90% of autistic and in 93% of schizophrenic patients. High titer IgA antibodies to gluten or casein were found in 30% of children with autism while in schizophrenic patients 86% had elevated IgA antibodies to gluten and 67% to casein; some normal children and adults have these antibodies but only in trace amounts. When schizophrenic patients were treated with dialysis or a gluten-casein free diet, or both (Cade, R., Wagemaker, H., Privette, R.M., Fregly, M., Rogers, J. and Orlando, J. (1990) Psychiatry: A World Prespective 1: 494–500) peptiduria and Brief Psychiatric Rating Scores fell while abnormal behavior diminished. A gluten-casein free diet was accompanied by improvement in 81% of autistic children within 3 months in most of the behavior categories. Our data provide support for the proposal that many patients with schizophrenia or autism suffer due to absorption of exorphins formed in the intestine from incomplete digestion of gluten and casein.

Central injection in rats of α-melanocyte-stimulating hormone analog: effects on food intake and brain Fos

Lateral cerebroventricular (LCVT) administration of the alpha-MSH agonist analog Nle4DPhe7alpha-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that alpha-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.

Dexfenfluramine induces fos-like immunoreactivity in discrete brain regions in rats

Administration of the anorectic agent, dexfenfluramine (DFEN) to rats induced dose- and time-dependent expression of Fos-like immunoreactivity in several discrete brain regions of rats. At moderate doses, the regions showing the most intense Fos immunostaining included the bed nucleus of the stria terminalis, the lateral part of the central amygdala, midline thalamic nuclei, habenular nuclei, lateral parabrachial nucleus, and nucleus of the solitary tract. It is suggested that these nuclei, many of which are known to receive gustatory or visceral input, may form part of a functional circuit via which DFEN modulates food intake. Rats that were made hungry by either food deprivation or administration of insulin also showed induction of Fos in several brain regions, but only that in the supramamillary/ventral tegmental area was suppressed by pretreatment with an anorectic dose of DFEN. The functional significance of these sites requires further investigation.

Sodium appetite: species and strain differences and role of renin-angiotensin-aldosterone system.

The characteristics of the appetite for NaCl in humans differ in some aspects from those in other species. The mechanisms of appetite for NaCl have been studied in detail in two species, rats and sheep. We review the treatments known to induce an appetite for NaCl in rats, with special reference to differences among strains in their spontaneous preference for NaCl solution. The current view of the mechanism is critically appraised, with particular emphasis on the role of angiotensin II, mineralocorticoids, cerebroventricular sodium transport, and the relation between preference for NaCl and the concentration of sodium in saliva. The appetite for NaCl in rodents other than rats is considered next, and reveals that mice, hamsters and gerbils are reluctant to ingest NaCl either spontaneously or after treatment with several of the natriorexigenic stimuli that are effective in rats. The characteristics of the appetite for NaCl in non-rodent species, including sheep, rabbit, dog, and non-human primates, are then described. We discuss some of the possible differences in mechanism that might account for this behavioral diversity among species.

c-fos expression in the rat brain following central administration of neuropeptide Y and effects of food consumption

Administration of neuropeptide Y (NPY) intracerebroventricularly (i.c.v.) results in the release of a number of hypothalamic and pituitary hormones and stimulation of feeding and suppression of sexual behavior. In this study, we sought to identify cellular sites of NPY action by evaluating perikaryal Fos-like immunoreactivity (FLI), a marker of cellular activation, in those hypothalamic and extrahypothalamic sites previously implicated in the control of neuroendocrine function and feeding behavior. Additionally, we compared the topography of FLI in these brain sites when food was either available ad libitum or withheld after NPY injection (1 nmol/3 microliters, i.c.v.). The results showed that one hour after NPY injection a larger number of cells in the parvocellular region of the paraventricular nucleus (PVN) were FLI-positive in the absence of food consumption. However, in association with food intake, a significant number of cells were intensely stained in the magnocellular region of the PVN. An analogous increase in FLI in association with feeding was apparent in the supraoptic nucleus (SON), the dorsomedial nucleus and the bed nucleus of the stria terminalis in the hypothalamus. Among the extrahypothalamic sites, feeding facilitated FLI in a large number of cells located in the lateral subdivision of the central amygdaloid nucleus and the lateral subdivision of the solitary tract. FLI was observed in a moderate number of cells in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, and this response was not changed by feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nonpeptide angiotensin receptor antagonists on water intake and salt appetite in rats.

Nonpeptide angiotensin AT-1 and AT-2 receptor antagonists were administered cerebroventricularly to rats and their effects on various types of angiotensin II (AII)-stimulated water and NaCl intakes examined. The AT-1 receptor blocker, losartan potassium (DUP 753), inhibited water intake evoked by central administration of AII, with the 50% inhibitory dose being less than 0.1 microgram. The functional inhibition by higher doses lasted at least 1 h. The AT-2 receptor antagonist PD 123319 also inhibited AII-induced water intake, but at doses about tenfold higher than losartan. Central, but not peripheral, administration of losartan partially inhibited NaCl intake induced by either sodium depletion, treatment with angiotensin converting enzyme inhibitors (CEIs), or adrenalectomy. PD 123319 partially inhibited NaCl intake induced by both sodium depletion and administration of CEI, but not after adrenalectomy. Another AT-2 receptor antagonist, CGP 42112A, likewise inhibited NaCl intake after sodium deprivation. These data suggest that both AT-1 and AT-2 receptor subtypes in the brain are involved in angiotensin-related water and NaCl intakes.

Effect of a nonpeptide angiotensin II receptor antagonist, DuP 753, on angiotensin-related water intake in rats☆

The effect of peripheral administration of the nonpeptide angiotensin II-1 (AII) receptor blocker, DuP 753, on the dipsogenic responses to peripherally administered angiotensins I, II, and III was tested. In all cases, DuP 753 significantly inhibited the drinking response, whether administered 15 or 45 minutes prior to administration of the dipsogen. These results suggest that the drinking responses to angiotensins I, II, and III are mediated by AII-1 receptors. They also suggest that either AIII acts via the AII-1 receptor or that DuP 753 competes at an AIII-sensitive receptor. These studies also showed that when both AII and DuP 753 were given cerebroventricularly (ICV), potent inhibition of the drinking response occurred. Further, when DuP 753 was administered peripherally and AII ICV, drinking was also inhibited. Hence, DuP 753 must penetrate the brain, at least at the circumventricular sites implicated in angiotensin-related drinking. However, centrally administered DuP 753 failed to inhibit the drinking response to peripherally administered AII. This observation is presently unexplained, but may be related to the possibility that centrally administered DuP 753 is inactivated more quickly than when it is administered peripherally. Additional studies will be required to assess this.

Glossopharyngeal Nerve Transection Eliminates Quinine-Stimulated Fos-Like Immunoreactivity in the Nucleus of the Solitary Tract: Implications for a Functional Topography of Gustatory Nerve Input in Rats

The relationship between specific gustatory nerve activity and central patterns of taste-evoked neuronal activation is poorly understood. To address this issue within the first central synaptic relay in the gustatory system, we examined the distribution of neurons in the nucleus of the solitary tract (NST) activated by the intraoral infusion of quinine using Fos immunohistochemistry in rats with bilateral transection of the chorda tympani (CTX), bilateral transection of the glossopharyngeal nerve (GLX), or combined neurotomy (DBLX). Compared with nonstimulated and water-stimulated controls, quinine evoked significantly more Fos-like-immunoreactive (FLI) neurons across the rostrocaudal extent of the gustatory NST (gNST), especially within its dorsomedial portion (subfield 5). Although the somatosensory aspects of fluid stimulation contributed to the observed increase in FLI neurons, the elevated number and spatial distribution of FLI neurons in response to quinine were remarkably distinguishable from those in response to water. GLX and DBLX produced a dramatic attenuation of quinine-evoked FLI neurons and a shift in their spatial distribution such that their number and pattern were indiscernable from those observed in water-stimulated controls. Although CTX had no effect on the number of quinine-evoked FLI neurons within subfield 5 at intermediate levels of the gNST, it produced intermediate effects elsewhere; yet, the spatial distribution of the quinine-evoked FLI neurons was not altered by CTX. These findings suggest that the GL provides input to all FLI neurons responsive to quinine, however, some degree of convergence with CT input apparently occurs in this subpopulation of neurons. Although the role of these FLI neurons in taste-guided behavioral responses to quinine remains speculative, their possible function in oromotor reflex control is considered.