The role of intraamygdaloid neurotensin and dopamine interaction in conditioned place preference.

Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test. Male Wistar rats were microinjected bilaterally with 100 ng NT or 2 µg D1 dopamine receptor antagonist alone, or D1 dopamine antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Other animals received 4 µg D2 dopamine receptor antagonist Sulpiride alone, or administration of D2 dopamine receptor antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Rats that received 100 ng NT spent significantly more time in the treatment quadrant during the test session. Pre-treatment with the D1 dopamine antagonist, blocked the effects of NT. D2 dopamine receptor antagonist pretreatment could prevent the positive reinforcing effects of NT as well. Antagonists themselves did not influence the place preference. Our results show that the rewarding effect of NT can be due to the modulation of DA system, since its effects could be blocked by either D1 dopamine or D2 dopamine antagonist preteatment.

Food and water intake, body temperature and metabolic consequences of interleukin-1ß microinjection into the cingulate cortex of the rat.

In order to elucidate whether cytokine mechanisms of the cingulate cortex (cctx) are important in the central regulation of homeostasis, in the present study, feeding-metabolic effects of direct bilateral microinjection of interleukin-1ß (IL-1ß) into the cctx of the rat have been investigated. Short- (2h), medium (12h) and long-term (24h) food and water intakes and body temperature were measured after the intracerebral administration of this primary cytokine or vehicle solution, with or without paracetamol pretreatment. The effect of IL-1ß on the blood glucose level of animals was examined in glucose tolerance test (GTT), and concentrations of relevant plasma metabolites (total cholesterol, HDL, LDH, triglycerides, uric acid) were additionally also determined following the above microinjections. In contrast to causing no major alteration in the food and water intakes, the cytokine treatment evoked significant increase in the body temperature of the rats. Prostaglandin-mediated mechanisms were shown to have important role in the mode of this action of IL-1ß, since paracetamol pretreatment partially prevented the development of the above mentioned hyperthermia. In the GTT, no considerable difference was observed between the blood glucose levels of the cytokine treated and control animals. Following IL-1ß microinjection, however, significant decrease of HDL and total cholesterol was found. Our present findings indicate that elucidating the IL-1ß mediated homeostatic control mechanisms in the cingulate cortex may lead to the better understanding not only the regulatory entities of the healthy organism but also those found in obesity, diabetes mellitus and other worldwide rapidly spreading feeding-metabolic disorders.

Impaired glucose tolerance after streptozotocin microinjection into the mediodorsal prefrontal cortex of the rat.

The mediodorsal prefrontal cortex (mdPFC) is a key structure of the central glucose-monitoring (GM) neural network. Previous studies indicate that intracerebral streptozotocin (STZ) microinjection-induced destruction of local chemosensory neurons results in feeding and metabolic alterations. The present experiments aimed to examine whether STZ microinjection into the mdPFC causes metabolic deficits. To do so, glucose tolerance test (GTT) and measurements of plasma metabolites were performed in STZ-treated or control rats. Intraperitoneal D-glucose load was delivered 20 min or 4 weeks following the intracerebral microinjection of STZ or saline (acute or subacute GTT, respectively). The STZ-treated rats displayed acute glucose intolerance: at the 120th min of the test, blood glucose level of these rats was significantly higher than that of the ones in the control group. When determining the plasma level of various metabolites, 30 min following the intracerebral STZ or saline microinjection, the triglyceride concentration of the STZ-treated rats was found to be reduced compared with that of the control rats. The GM neurons of the mdPFC are suggested to be involved in the organization of complex metabolic processes by which these chemosensory cells contribute to adaptive control mechanisms of the maintenance of homeostasis.