NMDA receptor function within the anterior piriform cortex and lateral hypothalamus in rats on the control of intake of amino acid-deficient diets.

Animals decrease intake of an indispensable amino acid (AA)-deficient or devoid diet, due in part to decreased dietary limiting AA (DLAA) concentrations within the anterior piriform cortex (APC), and to a recognition process that occurs as early as 20 min following exposure to AA deficiencies. Glutamate levels within the APC change in response to AA deficiencies. The APC projects to the lateral hypothalamus (LH), where glutamate acts to stimulate food intake. We hypothesize that the APC, through glutamatergic projections to the LH, inhibits the LH, which signals to reject the AA-deficient or devoid diet, and trigger aversions to the AA-deficient or devoid diet via an ascending pathway to the APC. We examined the effects of (1) bilateral APC and LH blockade of glutamate's NMDA receptors with the antagonist, D-AP5, (2) APC blockade of AMPA receptors with the antagonist, NBQX, to block glutamate transmission from the APC, and (3) direct injection of the agonist, NMDA, into the LH on intake of the AA-deficient, devoid, or corrected diet. Administration of D-AP5 into the APC increased intake of AA-deficient diet by 6 h, but D-AP5 in the LH decreased AA-devoid diet preferentially over AA corrected intake sooner. NBQX in the APC increased AA-deficient diet intake, also at 6 h. NMDA injection into the LH-stimulated intake of the AA corrected diet by 3 h, but did not affect AA-devoid diet intake. Thus, the glutamate receptors in the APC and LH are involved in the feeding responses to AA-deficient diet, albeit with regional differences. We suggest that glutamate mediates the anorectic responses to AA-deficient diets through recognition of AA-devoid diet with the glutamatergic output cells of the APC sending glutamate-based signals for changes in food intake within the LH and through learned avoidance of AA-deficient diet within the APC, as indicated through the more immediate and prolonged periods of activation within the LH and APC, respectively.

Effects of amino acid deficiency on monoamines in the lateral hypothalamus (LH) in rats.

Animals decrease intake of an indispensable amino acid deficient diet, due in part to decreased dietary limiting amino acid concentrations within the anterior piriform cortex (APC). In addition to studies supporting a primary role for the APC in this phenomenon, recent studies have shown that the lateral hypothalamus (LH), which receives projections from the APC, also mediates the anorectic response to amino acid deficiency. The neurochemical changes within the LH that accompany the anorexia to amino acid deficiency are unclear. We hypothesized that norepinephrine (NE), dopamine (DA) and serotonin, whose levels are altered in response to amino acid deficiency within the APC, also act within the LH to mediate amino acid deficiency-induced anorexia. We determined that ingestion of an amino acid devoid diet increased concentrations of NE and the serotonin metabolite, 5-hydroxyindoleacetic acid in the LH. The 5-hydroxytryptamine metabolite was increased overall, according to analysis by area under the curve. Individual points reached significance at 130 min; NE was elevated at 170 min. These results suggest that the sustained anorectic response following ingestion of an amino acid devoid diet may be associated with increased activity of the NE and 5-hydroxytryptamine systems in the LH.

The rapid anorectic response to a threonine imbalanced diet is decreased by injection of threonine into the anterior piriform cortex of rats.

Rats quickly recognize and reject diets deficient in an essential amino acid. The purpose of this study was to determine whether the anterior piriform cortex (APC), the site traditionally recognized as the amino acid chemosensor, plays a role in this early behavior. Rats had cannulae implanted bilaterally into the APC, and were injected with either saline vehicle or 2 nmoles of threonine (n = 6 per group). All rats were then fed a diet imbalanced with respect to threonine. The threonine-injected group had first meals of longer duration and consumed more food. These data conformed to expectations derived from earlier studies of responses to the first meal of an amino acid imbalanced diet. We conclude that the concentration of the dietary limiting amino acid in the APC regulates acceptance and rejection of amino acid deficient diets.

DMSO as a vehicle for central injections: tests with feeding elicited by norepinephrine injected into the paraventricular nucleus.

Dimethyl sulfoxide (DMSO) is becoming increasingly popular as a vehicle in studies employing central injections. The aim of the present study was to determine whether the vehicle required for solubilization of substances for central injection [75% DMSO and 25% artificial CSF (aCSF)] would alter the well-characterized stimulatory response to norepinephrine (NE) injected into the paraventricular nucleus (PVN) on short-term food intake. To evaluate its suitability, we compared the effects of repeated unilateral injections of NE dissolved in two different vehicles (100% aCSF or 75% DMSO, 25% aCSF), in separate groups of animals every 48 h over a 30-day period. NE (40 nmol) stimulated food intake by approximately sevenfold compared to either vehicle alone, and the stimulatory effect was similar whether aCSF or 75% DMSO was used as a vehicle. Furthermore, the NE-induced feeding did not vary in magnitude across a series of 13 tests. These results suggest that 75% DMSO is a suitable vehicle for administering NE (and likely other water-insoluble substances)in small volumes of 0.3 microl into specific brain regions.