Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The widespread and abundant distribution of P2Y receptors in the mammalian brain suggests important functions for these receptors in the CNS. To study a possible involvement of the P2Y receptors in the regulation of fear and anxiety, the influences of the P2Y(1,11,12) receptor-specific agonist adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS), the P2X(1,3) receptor agonist alpha,beta-methylene ATP (alpha,betameATP), the unspecific P2 receptor antagonist pyridoxalphosphate-6-azopheny l-2',4'-disulfonic acid (PPADS), and the specific P2Y(1) receptor antagonist N(6)-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS 2179) on the elevated plus-maze behavior of the rat were investigated. All tested compounds were given intracerebroventricularly (0.5 microl). ADPbetaS (50 and 500 fmol) produced an anxiolytic-like behavioral profile reflected by an increase of the open arm exploration. The anxiolytic-like effects were antagonized by pretreatment with PPADS (5 pmol) or MRS 2179 (5 pmol). Both compounds caused anxiogenic-like effects when given alone. Furthermore, the anxiolytic-like effects of ADPbetaS could be antagonized by pretreatment with the nitric oxide synthase (NOS) inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME). In addition, the anxiogenic-like effects of PPADS were reversed by the pretreatment with L-arginine (500 pmol), which is the natural substrate for NOS, but not by D-arginine (500 pmol), which is not. Immunofluorescence staining revealed the presence of P2Y(1) receptors on neurons in different brain regions such as hypothalamus, amygdala, hippocampus and the periaqueductal gray. Furthermore, the colocalization of P2Y(1) receptors and neuronal NOS (nNOS) on some neurons in these regions could be demonstrated. The highest density of P2Y(1)- and nNOS-immunoreactivity was detected in the dorsomedial hypothalamic nucleus. Taken together, the present results suggest that P2Y(1) receptors are involved in the modulation of anxiety in the rat. The anxiolytic-like effects after stimulation of P2Y(1) receptors seem to be in close connection with the related nitric oxide production.
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PMID:Stimulation of P2Y1 receptors causes anxiolytic-like effects in the rat elevated plus-maze: implications for the involvement of P2Y1 receptor-mediated nitric oxide production. 1262 23

The involvement of dopaminergic mechanisms in fear and anxiety is still unclear. Behavioral studies aimed to disclose the involvement of dopamine in anxiety have reported anxiolytic-like, anxiogenic-like and lack of effects with the use of dopaminergic agonists and antagonists in animal models of anxiety. This work was an attempt to contribute to this field by providing evidence that these discrepancies may be due to the kind of aversive situation the animals experience in these models. The present study examined the effects of a dopaminergic agonist apomorphine, a dopaminergic D(1) antagonist SCH 23390 and a D(2) receptor antagonist sulpiride on the two-way avoidance response test (CAR) and on the switch-off responses to light (SOR). In both tests, learning was assessed by the performance of the animals across four blocks of 10 trials in which light was paired to footshocks (CAR) or only light was presented to the animals (SOR). The obtained data show that rats learn to make a shuttling response to avoid the shock in the CAR test and maintain a regular pace of switch-off responses in the SOR. While sulpiride and SCH 23390 administrations prevented learning of the avoidance responses, apomorphine injections produced a dose-dependent enhancement in the conditioned learning in the CAR test. The number of escape responses was unchanged by these drugs. In the light-induced switch-off test, apomorphine reduced the number of switch-off responses whereas sulpiride increased these responses. These findings suggest that the involvement of dopaminergic mechanisms in threatening situations depends on the nature of the aversive stimulus. Activation of D(1) and D(2) receptors seems to be implicated in the heightened aversiveness to conditioned stressful situations, as assessed by the CAR test. Thus, blockade of D(1) and D(2) receptors may be necessary for attenuating the aversiveness triggered by these conditioned fear stimuli. In contrast, mechanisms mediated by D(2) receptors seem to be involved in the setting up of adaptive responses to innate fear reactions. Therefore, the signal of the modulatory dopaminergic mechanisms on defensive behavior will depend on the type of emotional stimuli triggering the coping reaction.
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PMID:Dopaminergic mechanisms in the conditioned and unconditioned fear as assessed by the two-way avoidance and light switch-off tests. 1550 13