Sensitivity of food reward-representing neurons in the mSh-Nac determines the level of satisfaction that governs cessation of consumption, probably through connections with the LHA. D1R signaling is a key element in this function, and is impaired in obesity-prone rats.

This study was designed to test the hypothesis of whether activation of presynaptic P2X receptor-gated ion channels elicits noradrenaline release from central catecholaminergic terminals. ATP, ␣,␤-methylene-adenosine 5Ј-triphosphate (␣,␤-methyleneATP), and ADP elicited concentration-dependent [ 3 H]noradrenaline outflow from superfused rat hippocampal slices with the following rank order of agonist potency: ␣,␤-methyleneATP Ͼ ATP Ͼ ADP. Among P2 receptor antagonists, pyridoxal-phosphate-6-azophenyl-2Ј,4Ј-disulphonic acid (30 M), 4,4Ј,4ЈЈ,4ЈЈЈ-[carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid (100 nM), and 8,8Ј-[carbonybis(imino-3,1-phenylenecarbonylimino)]bis1,3,5-naphthalenetrisulphonic acid (10 M) significantly inhibited the outflow of [ 3 H]noradrenaline, evoked by ATP, whereas Brilliant Blue G (100 nM), 2Ј-deoxy-N 6 -methyladenosine 3Ј,5Ј-bisphosphate tetraammonium (10 M), the A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (250 nM), and the A 2A receptor antagonist 3,7-dimethyl-1-propargylxanthine (250 nM) were ineffective. Pretreatment with the G i protein inhibitor pertussis toxin (2.5 g/ml) did not change the effect of ATP on [ 3 H]noradrenaline outflow. In contrast, a decrease in extracellular pH from 7.4 to 6.6 significantly attenuated the response by ATP. When extracellular Na ϩ was replaced by choline chloride and in the presence of the noradrenaline uptake inhibitor desipramine (10 M), the ATP-evoked [ 3 H]noradrenaline outflow was almost completely abolished, indicating that its underlying mechanism is the sodium-dependent reversal of the noradrenaline transporter. Reverse transcription-polymerase chain reaction analysis revealed that mRNA encoding P2X 1 , P2X 2 , P2X 3 , P2X 4 , P2X 6 , P2X 7 , and P2Y 1 receptor subunits were expressed in the brainstem containing catecholaminergic nuclei projecting to the hippocampus, whereas mRNA encoding P2X 5 , P2Y 2 , P2Y 4 , and P2Y 6 receptors were absent. Taken together, these results indicate that noradrenergic terminals of the rat hippocampus are equipped with presynaptic facilitatory P2X receptors, displaying a pharmacological profile similar to homomeric P2X 1 and P2X 3 receptors.

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naïve animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems.

No abstract

Vasopressin influences social behaviour in mammals, in particular social recognition and bonding. However, much less is known about its avian analogue, vasotocin, although vasotocin appears to modulate singing behaviour and agonistic interactions together with vasoactive intestinal peptide (VIP) in some songbirds. The objectives of our study were to compare the expression of vasotocin and VIP in brain nuclei hypothetised to be part of the social behavioural network, i.e. septal areas, bed nucleus of the stria terminalis and medial preoptic nucleus (POM), in two songbird species in the wild: the blue tit (Cyanistes caeruleus) and European penduline tit (Remiz pendulinus). These two closely related passerine birds differ in their pair bonding and mating systems: blue tits are socially monogamous with extensive pair bond lasting for several months, whereas in the European penduline tit, pair bond is short and it dissolves during or after laying of the eggs. The two species did not differ in the distribution of vasotocin in the observed brain regions; however, VIP was more abundant in all three regions of penduline tits than in blue tits. We found a sex difference in favour of males in the distribution of vasotocin- and VIP-immunoreactive neurones, fibres and terminals in all three regions in penduline tits. In blue tits, such gender differences were only observed in the POM. The limited differences between the two species suggest that the levels of vasotocin and VIP in the socially relevant brain regions are likely influenced by many other social or environmental factors than just by differences in the duration of pair bonding.