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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Sustained antagonism of acute ethanol-induced ataxia following microinfusion of cyclic AMP and cpt-cAMP in the mouse cerebellum.
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Sustained antagonism of acute ethanol-induced ataxia following microinfusion of cyclic AMP and cpt-cAMP in the mouse cerebellum.

机译：在小鼠小脑中微量注入环状AMP和cpt-cAMP后，急性乙醇引起的共济失调的持续拮抗作用。

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Ataxia is a conspicuous physical manifestation of alcohol consumption in humans and laboratory animals. Previously we reported possible involvement of cAMP in ethanol-induced ataxia. We now report a sustained antagonism of ataxia due to multiple ethanol injections following intracerebellar (ICB) cAMP or cpt-cAMP microinfusion. Adenylyl cyclase drugs cAMP, cpt-cAMP, Sp-cAMP, Rp-cAMP, adenosine A agonist, N-cyclohexyladenosine (CHA) and GABA(A) agonist muscimol were directly microinfused into the cerebellum of CD-1 male mice to evaluate their effect on ethanol (2 g/kg; i.p.) ataxia. Drug microinfusions were made via stereotaxically implanted stainless steel guide cannulas. Rotorod was used to evaluate the ethanol's ataxic response. Intracerebellar cAMP (0.1, 1, 10 fmol) or cpt-cAMP (0.5, 1, 2 fmol) 60 min before ethanol treatment, dose-dependently attenuated ethanol-induced ataxia in general agreement with previous observations. Intracerebellar microinfusion of cAMP (100 fmol) or cpt-cAMP (2 fmol) produced a sustained attenuation of ataxia following ethanol administration at 1, 4, 7 and 25 h or 31 h post-cAMP/cpt-cAMP microinfusion. At 31 h post-cAMP, the ataxic response of ethanol reappeared. Additionally, marked antagonism to the accentuation of ethanol-induced ataxia by adenosine A and GABA(A) agonists, CHA (34 pmol) and muscimol (88 pmol), respectively, was noted 24h after cAMP and cpt-cAMP treatment. This indicated possible participation of AC/cAMP/PKA signaling in the co-modulation of ethanol-induced ataxia by A adenosinergic and GABAergic systems. No change in normal motor coordination was noted when cAMP or cpt-cAMP microinfusion was followed by saline. Finally, Rp-cAMP (PKA inhibitor, 22 pmol) accentuated ethanol-induced ataxia and antagonized its attenuation by cAMP whereas Sp-cAMP (PKA activator, 22 pmol) produced just the opposite effects, further indicating participation of cAMP-dependent PKA downstream. Overall, the results support a role of AC/cAMP/PKA signaling in the expression of ethanol-induced ataxia and its co-modulation by adenosine A and GABA(A) receptors.
机译：共济失调是人类和实验动物饮酒的明显物理表现。以前我们报道了cAMP可能参与乙醇诱导的共济失调。现在，我们报告由于脑内（ICB）cAMP或cpt-cAMP微输注后多次乙醇注射而导致的共济失调持续拮抗作用。将腺苷酸环化酶药物cAMP，cpt-cAMP，Sp-cAMP，Rp-cAMP，腺苷A激动剂，N-环己基腺苷（CHA）和GABA（A）激动剂麝香酚直接微注入CD-1雄性小鼠小脑以评估其作用乙醇（2 g / kg; ip）共济失调。通过立体定位植入的不锈钢引导插管进行药物微输注。使用Rotorod评估乙醇的共轭反应。乙醇治疗前60分钟，小脑内cAMP（0.1，1，10 fmol）或cpt-cAMP（0.5，1，2 fmol），剂量依赖性地减轻了乙醇引起的共济失调，这与以前的观察结果基本一致。在cAMP / cpt-cAMP微输注后的1、4、7和25 h或31 h给予乙醇后，对cAMP（100 fmol）或cpt-cAMP（2 fmol）的脑内微输注产生持续的共济失调减弱。在cAMP后31小时，乙醇的共轭反应再次出现。此外，在cAMP和cpt-cAMP处理后24小时，腺苷A和GABA（A）激动剂分别对CHA（34 pmol）和muscimol（88 pmol）增强乙醇诱导的共济失调有明显的拮抗作用。这表明AC / cAMP / PKA信号可能参与了腺苷能和GABA能系统对乙醇诱导的共济失调的共调节。当cAMP或cpt-cAMP微输注后加生理盐水时，未观察到正常运动协调的变化。最后，Rp-cAMP（PKA抑制剂，22 pmol）加重了乙醇诱导的共济失调，并通过cAMP拮抗了共济失调，而Sp-cAMP（PKA激活剂，22 pmol）产生了相反的作用，进一步表明了下游依赖cAMP的PKA的参与。总体而言，结果支持AC / cAMP / PKA信号在乙醇诱导的共济失调的表达及其由腺苷A和GABA（A）受体的共调节中的作用。

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