The inhibitory effect of trimethylamine on the anticonvulsant activities of quinine in the pentylenetetrazole model in rats
ABSTRACT Quinine specifically blocks connexin 36 (Cx36), one of the proteins that form gap junction channels. Quinine suppressed ictal epileptiform activity in in vitro and in vivo studies without decreasing neuronal excitability. In this study, we considered the possible mechanism of anticonvulsant effects of quinine (1, 250, 500, 1000 and 2000 microM, i.c.v.) in the pentylenetetrazole (PTZ) model of seizure. Thus, we used trimethylamine (TMA) (0.05 microM, 5 microM, 50 microM), a gap junction channel opener, to examine whether it could reverse the effects of quinine in rats. Intracerebroventricular (i.c.v.) injection of quinine affected generalized tonic-clonic seizure (GTCS) induced by PTZ by increments in seizure onset and reducing seizure duration. Additionally, pretreatment with different doses of TMA (i.c.v.) attenuated the anticonvulsant effects of quinine on the latency and duration of GTCS. It can be concluded that quinine possesses anticonvulsant effects via modulation of gap junction channels, which could contribute to the control of GTCS.
SourceAvailable from: Javier Franco-Pérez[Show abstract] [Hide abstract]
ABSTRACT: Mefloquine can cross the blood-brain barrier and block the gap junction intercellular communication in the brain. Enhanced electrical coupling mediated by gap junctions is an underlying mechanism involved in the generation and maintenance of seizures. For this reason, the aim of this study was to analyze the effects of the systemic administration of mefloquine on tonic-clonic seizures induced by two acute models such as pentylenetetrazole and maximal electroshock. All the control rats presented generalized tonic-clonic seizures after the administration of pentylenetetrazole. However, the incidence of seizures induced by pentylenetetrazole significantly decreased in the groups administered systematically with 40 and 80 mg/kg of mefloquine. In the control group, none of the rats survived after the generalized tonic-clonic seizures induced by pentylenetetrazole, but survival was improved by mefloquine. Besides, mefloquine significantly modified the total spectral power as well as the duration, amplitude and frequency of the epileptiform activity induced by pentylenetetrazole. For the maximal electroshock model, mefloquine did not change the occurrence of tonic hindlimb extension. However, this gap junction blocker significantly decreased the duration of the tonic hindlimb extension induced by the acute electroshock. These data suggest that mefloquine at low doses might be eliciting some anticonvulsant effects when is systemically administered to rats.BMC Neuroscience 03/2015; 16(7). DOI:10.1186/s12868-015-0145-7 · 2.85 Impact Factor
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ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disease characterized by akinesia, bradykinesia, resting tremors and postural instability. Although various models have been developed to explain basal ganglia (BG) pathophysiology in PD, the recent reports that dominant beta (β) oscillations (12–30 Hz) in BG nuclei of PD patients and parkinsonian animals coincide with motor dysfunction has led to an emerging idea that these oscillations may be a characteristic of PD. Due to the recent realization of these oscillations, the cellular and network mechanism(s) that underlie this process remain ill-defined. Here, we postulate that gap junctions (GJs) can contribute to β oscillations in the BG of hemiparkinsonian rats and inhibiting their activity will disrupt neuronal synchrony, diminish these oscillations and improve motor function. To test this, we injected the GJ blockers carbenoxolone (CBX) or octanol in the right globus pallidus externa (GPe) of anesthetized hemiparkinsonian rats and noted whether subsequent changes in β oscillatory activity occurred using in vivo electrophysiology. We found that systemic treatment of 200 mg/kg CBX attenuated normalized GPe β oscillatory activity from 6.10 ± 1.29 arbitrary units (A.U.) (pre-CBX) to 2.48 ± 0.87 A.U. (post-CBX) with maximal attenuation occurring 90.0 ± 20.5 min after injection. The systemic treatment of octanol (350 mg/kg) also decreased β oscillatory activity in a similar manner to CBX treatment with β oscillatory activity decreasing from 3.58 ± 0.89 (pre-octanol) to 2.57 ± 1.08 after octanol injection. Next, 1 μl CBX (200 mg/kg) was directly injected into the GPe of anesthetized hemiparkinsonian rats; 59.2 ± 19.0 min after injection, β oscillations in this BG nucleus decreased from 3.62 ± 1.17 A.U. to 1.67 ± 0.62 A.U. Interestingly, we were able to elicit β oscillations in the GPe of naive non-parkinsonian rats by increasing GJ activity with 1 μl trimethylamine (TMA, 500 nM). Finally, we systemically injected CBX (200 mg/kg) into hemiparkinsonian rats which attenuated dominant β oscillations in the right GPe and also improved left forepaw akinesia in the step test. Conversely, direct injection of TMA into the right GPe of naive rats induced contralateral left forelimb akinesia. Overall, our results suggest that GJs contribute to β oscillations in the GPe of hemiparkinsonian rats.Experimental Neurology 01/2015; 265. DOI:10.1016/j.expneurol.2015.01.004 · 4.62 Impact Factor
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ABSTRACT: In this study, the influences of the gap junction blocker quinine and the gap junction opener trimethylamine (TMA) in antinociception were examined using the formalin test as a model of pain. We found that quinine was dose-dependently antinociceptive in both the early and late phases of the formalin test. In contrast, TMA alone did not change the nociceptive threshold in the formalin test. In the both phases of the formalin test, TMA increased antinociception of quinine. It couldn't conclude that gap junction blockade plays role in the mechanism by which quinine suppresses pain responses in the formalin test. Furthermore, it seems that pretreatment with TMA has additive effects on the antinociceptive effect of quinine in the formalin test.