کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6257899 1612962 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Blockade of the metabotropic glutamate (mGluR2) modulates arousal through vigilance states transitions: Evidence from sleep–wake EEG in rodents
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Blockade of the metabotropic glutamate (mGluR2) modulates arousal through vigilance states transitions: Evidence from sleep–wake EEG in rodents
چکیده انگلیسی


• mGluR2 signalling is believed to have potential for treatment of psychiatric disorders.
• mGluR2 blockade elicits arousal associated with enhanced theta/gamma oscillations.
• Blockade of mGluR2 induced different arousal profile as compared with classical psychostimulant.
• mGluR2 blockade-induced arousal was confirmed in WT but not mGluR2 (−/−) mice.
• Inactivation of mGluR2 plays a role in cortical arousal and transitions from sleep to waking.

Accumulating data continue to support the therapeutic potential of glutamate metabotropic (mGluR2) receptors for treatment of psychiatric disorders such as depression, anxiety and schizophrenia. Glutamate neurotransmission is an integral component of sleep–wake mechanisms, which have translational relevance to assess on-target activity of drugs. Here, we investigated the influence of mGluR2 inactivation upon sleep–wake electroencephalogram (EEG) in rodents. Rats were administered with vehicle, the specific mGluR2 antagonist LY341495 (2.5, 5, 10 mg/kg) or negative allosteric modulator (NAM) Ro-4491533 (2.5, 10 and 40 mg/kg) at lights onset. mGluR2 (−/−) mice were used to confirm the selectivity of functional response. Both LY341495 and Ro-4491533 induced an immediate and endured desynchronized cortical activity during 3–6 h associated with enhanced theta and gamma oscillations and depressed slow oscillations during sleep. The arousal-promoting effect is consistent with the marked lengthening of sleep onset latency, an increased number of state transitions from light sleep to waking and the gradual increase in homeostatic compensatory sleep. The arousal response to mGluR2 blockade was not accompanied by sharp rebound hypersomnolence as found with the classical psycho-stimulant amphetamine. mGluR2 (−/−) mice and their WT littermates exhibited similar sleep–wake phenotype, while Ro-4491533 (40 mg/kg) enhanced waking associated with increased locomotor activity and body temperature in WT but not in mGluR2 (−/−) mice, which confirm the role of mGluR2 inactivation in the arousal response. Our results lend support for a role of mGluR2 blockade in promoting cortical arousal associated with theta/gamma oscillations as well as high thresholds transitions from sleep to waking.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 270, 15 August 2014, Pages 56–67