Exogenous neuropeptide Y (NPY) reduces experimental anxiety in a wide range of animal models. The generation of an NPYtransgenic rat has provided a unique model to examine the role of endogenous NPY in control of stress and anxiety-related behaviors using paradigms previously used by pharmacological studies. Locomotor activity and baseline behavior on the elevated plus maze were normal in transgenic subjects. Two robust phenotypic traits were observed. (i) Transgenic subjects showed a markedly attenuated sensitivity to behavioral consequences of stress, in that they were insensitive to the normal anxiogenic-like effect of restraint stress on the elevated plus maze and displayed absent fear suppression of behavior in a punished drinking test. (ii) A selective impairment of spatial memory acquisition was found in the Morris water maze. Control experiments suggest these traits to be independent. These phenotypic traits were accompanied by an overexpression of prepro-NPY mRNA and NPY peptide and decreased NPY-Y1 binding within the hippocampus, a brain structure implicated both in memory processing and stress responses. Data obtained using this unique model support and extend a previously postulated anti-stress action of NPY and provide novel evidence for a role of NPY in learning and memory.anxiety ͉ amygdala N europeptide Y (NPY) (1) is highly expressed in the mammalian brain. Its pharmacological administration into the central nervous system reduces experimental anxiety in a wide range of animal models (2-5), but its involvement in memory function is less clear. NPY receptors cloned to date all belong to the superfamily of G protein-coupled receptors but differ in their ligand affinity profiles. The NPY-Y1 receptor (6-8) requires the intact NPY sequence for recognition and activation, and seems to be the subtype mediating anti-anxiety actions of NPY (3-5, 9, 10). The Y2 receptor subtype is also activated by C-terminal fragments of NPY, such as NPY 13-36 (11). The highest number of NPY-binding sites, predominantly of the Y2 subtype, is found within the hippocampus. Activation of Y2 receptors within this structure has been shown to suppress hippocampal glutamatergic transmission through presynaptic mechanisms (12, 13), but the behavioral consequences of Y2 signaling in this area are unclear.In agreement with anti-stress effects observed following central administration of NPY, a role for endogenous NPY in control of stress and anxiety-related behaviors is suggested by several findings. Acute physical restraint, which promotes experimental anxiety (14), suppresses NPY mRNA and peptide levels within the amygdala and cortex. In contrast, repeated exposure to the same stressor once daily for 10 days leads to a complete behavioral and endocrine habituation, accompanied by an up-regulation of amygdala NPY expression (15). We have therefore proposed that an up-regulation of NPY expression may contribute to the behavioral adaptation to stress. This extends a hypothesis that NPY may act to ''buffer'' behavioral effects of st...

The systemic intraperitoneal (i.p.) The systemic administration of adenosine agonists in rodents has been shown to induce a pronounced dosedependent depression of spontaneous motor activity (Vapaatalo et al. 1975;Snyder et al. 1981;Durcan and Morgan 1989;Heffner et al. 1989;Nikodijevic et al. 1991;Jacobson et al. 1993;Ferre et al. 1994a). This behavioral effect is most probably mediated at the central level, since it is also induced after their intraventricular or intracerebral administration (Barraco et al. 1983(Barraco et al. , 1993. Furthermore, the administration of an adenosine antagonist which poorly penetrates the blood-brain barrier could not counteract an adenosine agonist-induced motor depression (Durcan and Morgan 1989b;Nikodijevic et al. 1991

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Background-Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at μ-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors.