Balázs Lukáts

Single neuron activity changes to interleukin-1β in the orbitofrontal cortex of the rat

The orbitofrontal cortex (OBF) is known to play important roles in various regulatory processes. Our preliminary behavioral studies showed homeostatic alterations after orbitofrontal cortical microinjection of interleukin-1beta (IL-1beta) in the rat. To elucidate whether the above alterations were due to direct neuronal action of the cytokine, extracellular single neuron activity was recorded in the OBF of anesthetized rats by means of tungsten fiber multibarreled glass microelectrodes during microelectrophoretic administration of IL-1beta. More than half (56%) of all cells tested changed in firing rate in response to IL-1beta. Approximately 90% of these cytokine-modulated neurons were also sensitive to microelectrophoretically applied d-glucose, that is, proved to be the elements of the central glucose-monitoring neural network. The present findings demonstrate that IL-1beta can exert direct modulatory role on neurons in the OBF.

Homeostatic alterations induced by interleukin-1β microinjection into the orbitofrontal cortex in the rat

The present experiments were designed to elucidate the effect of direct orbitofrontal cortical administration of interleukin-1beta (IL-1beta) on the homeostatic regulation. Short- and long-term food intakes (FI), water intakes and body temperature (BT) were measured before and after a bilateral microinjection of IL-1beta (with or without paracetamol /P/ pretreatment) into the orbitofrontal cortex (OBF) of Wistar rats, and the effects were compared with those found in vehicle-treated and i.p. injected IL-1beta, IL-1beta+P or control animals. In addition, blood glucose levels (BGLs), along a glucose tolerance test, and plasma concentrations of insulin, leptin, cholesterol, triglycerides and urate were determined in cytokine treated and control rats. Short-term FI was suppressed after orbitofrontal cortical or peripheral application of IL-1beta. In the long-term FI, however, there was no significant difference among the groups. Cytokine microinjection into the OBF, similar to the i.p. administration, was also followed by a significant increase in BT. Pretreatment with P failed to influence the anorexigenic and hyperthermic effects of the centrally administered IL-1beta. The sugar load led to a diabetes-like prolonged elevation of BGL in the IL-1beta treated animals. Following cytokine administration, plasma levels of insulin and that of triglycerides were found decreased, whereas that of uric acid increased. The present findings confirm that the OBF is one of the neural routes through which IL-1beta exerts modulatory effect on the central homeostatic regulation.

Homeostatic alterations after IL-1β microinjection into the nucleus accumbens of the rat

The present study investigates the effects of direct administration of interleukin-1beta (IL-1beta) into the nucleus accumbens (NAcc) on homeostatic regulation. Short- and long-term food intakes (FI), water intakes (WI) and body temperature (BT) were measured before and after bilateral microinjection of IL-1beta (with or without paracetamol pretreatment) into the NAcc of Wistar rats, and the effects were compared with those found in vehicle treated control animals. In addition, blood glucose levels, along with a glucose tolerance test (GTT), and plasma concentrations of metabolic parameters, such as total cholesterol, triglycerides, HDL, LDL and uric acid were determined in cytokine treated and control rats. Short-term FI and WI were suppressed after intraaccumbens application of IL-1beta. A significant increase of BT was also observed after the cytokine microinjection. Pretreatment with paracetamol failed to influence the anorexigenic, adipsogenic, and pyrogenic effects of IL-1beta. A definite glucose intolerance of the cytokine treated animals and their pathologically elevated blood glucose levels became obvious in the acute GTT. Following IL-1beta microinjection, plasma levels of triglycerides, total cholesterol and LDL were found increased. Our present findings show that the NAcc is an important site of action of IL-1beta mediated processes in central homeostatic regulation.

Homeostatic alterations after intrapallidal microinjection of interleukin-1β in the rat

To elucidate the homeostatic consequences of direct pallidal administration of interleukin-1beta (IL-1beta), short- (2 h) and long-term (12 h) food intakes, water intake and body temperature were measured after bilateral microinjection of IL-1beta (with or without paracetamol/PAR/pretreatment) into the ventro-medial part of the globus pallidus (GP). The effects were compared with those found in vehicle- or vehicle+PAR-treated control animals and intraperitoneally (i.p.) injected IL-1beta, IL-1beta+PAR or control rats. Direct GP microinjection of IL-1beta, similar to the peripheral (i.p.) administrations, reduced remarkably short-term food intake in food deprived animals. However, there were no significant differences among the groups in long-term food intakes and in water intakes as well. IL-1beta microinjection into the GP caused a significant increase in body temperature. This IL-1beta induced hyperthermia was attenuated by PAR pretreatment, whereas food intake was not affected. Results of the electrophysiological experiments revealed substantial changes in GP extracellular single neuron activity in response to the microelectrophoretic administration of IL-1beta. The present findings, along with previous data, are discussed in terms of the glucose-monitoring neural circuitry through which cytokines exert their direct modulatory effect on central homeostatic regulation.

Taste reactivity deficit in anorexia nervosa.

Aim:  Anorexia nervosa is a complex psychiatric disorder posing a rapidly increasing burden on modern societies. Our purpose was to clarify perceptual‐motivational aspects of gustatory disturbances in the disease.

Taste reactivity alterations after IL-1β microinjection into the ventromedial hypothalamic nucleus of the rat

The ventromedial hypothalamic nucleus (VMH) is a central site of action of interleukin-1beta (IL-1beta) induced feeding disturbances. This study was designed to elucidate taste-related perceptual and motivational processes potentially contributing to the anorexia and adipsia seen after bilateral IL-1beta microinjection into the VMH. A saccharin conditioned taste aversion (CTA) paradigm was tested after the central IL-1beta administration. To further investigate whether gustatory deficits are involved in development of the feeding alterations, IL-1beta induced changes of taste responsiveness were also studied in taste reactivity tests. Administration of the cytokine into the VMH did not cause the development of CTA. During taste reactivity tests, however, IL-1beta treated rats displayed significantly poorer ingestive reactions to pleasant taste stimuli than did animals of the control group. In addition, the aversive responses of IL-1beta injected rats to pleasant tastes were significantly more robust than those of control animals. The cytokine treated animals also showed stronger aversion than ingestion to hedonically positive tastes. The present findings indicate that (1) anorexigenic and adipsogenic consequences of IL-1beta microinjection into the VMH are not due to development of cytokine induced CTA; and (2) hedonic responsiveness to palatable tastes is processed by IL-1beta mediated neural mechanisms in the VMH.