کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5816245 1115595 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of the cyclic-AMP/PKA cascade and of P/Q-type Ca++ channels in endocannabinoid-mediated long-term depression in the nucleus accumbens
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Role of the cyclic-AMP/PKA cascade and of P/Q-type Ca++ channels in endocannabinoid-mediated long-term depression in the nucleus accumbens
چکیده انگلیسی

Glutamate transmission between prefrontal cortex (PFC) and accumbens (NAc) plays a crucial role in the establishment and expression of addictive behaviors. At these synapses exogenous cannabinoid receptor 1 (CB1R) agonists reversibly inhibit excitatory transmission, and the sustained release of endogenous cannabinoids (eCB) following prolonged cortical stimulation leads to long-term depression (LTD). Activation of presynaptic K+ channels mediates the effects of exocannabinoids, but the transduction pathway underlying the protracted phase of eCB-LTD is unknown. Here we report that the maintenance of eCB-LTD does not involve presynaptic K+ channels: eCB-LTD was not affected by blockade of K+ channels with 4-AP (100 μM) and BaCl2 (300 μM) (fEPSP = 78.9 ± 5.4% of baseline 58-60 min after tetanus, compared to 78.9 ± 5.9% in control slices). In contrast, eCB-LTD was blocked by treatment of the slices with the adenylyl cyclase (AC) activator forskolin (10 μM), and with the protein kinase A (PKA) inhibitor KT5720 (1 μM) (fEPSP = 108.9 ± 5.7% in forskolin and 110.5 ± 7.7% in KT5720, compared to 80.6 ± 3.9% in control conditions). Additionally, selective blockade of P/Q-type Ca2+ channels with ω-agatoxin-IVA (200 nM) occluded the expression of eCB-LTD (fEPSP = 113.4 ± 15.9% compared to 78.6 ± 4.4% in control slices), while blockade of N- with ω-conotoxin-GVIA (1 μM) or L-type Ca2+ channels with nimodipine (1 μM), was without effect (fEPSP was 83.7 ± 5.3% and 87 ± 8.9% respectively). These data show that protracted inhibition of AC/PKA activity and P/Q-type Ca2+ channels are necessary for expression of eCB-LTD at NAc synapses.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 54, Issue 1, January 2008, Pages 87-94
نویسندگان
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