Intra-VTA CART 55-102 reduces the locomotor effect of systemic cocaine in rats: An isobolographic analysis
Intra-VTA CART 55-102 reduces the locomotor effect of systemic cocaine in rats: An isobolographic analysis
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DOI：
10.1016/j.npep.2006.12.003
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发表时间：
2007-04-01
期刊：
影响因子：
2.9
通讯作者：
Kuhar, Michael J.
中科院分区：
文献类型：
--
作者：
Jaworski, Jason N.;Kimmel, Heather L.;Kuhar, Michael J.
CART（可卡因和安非他明调节转录）肽似乎是精神兴奋剂药物的介质或调节剂。伏隔核中一个有趣的结果是，注射CART肽本身对运动活动没有影响，但它会降低可卡因或安非他明引起的运动活动。然而，在腹侧被盖区（VTA），注射CART肽已被证明可以增加运动活动，尽管程度较低[Kimmel， h.l., Gong， W., Vechia, s.d., Hunter, r.g., Kuhar, m.j., 2000]。腹侧被盖区注射可卡因和安非他明调控的转录肽55-102可诱导大鼠运动活动并促进条件位置偏好。j .杂志。[j].自然科学进展，1999,8(2):1 -7。本研究旨在阐明vta内CART 55-102和全身可卡因对运动活动的相互作用。cart -可卡因的相互作用已经用严格的等容积法进行了检验。这种类型的分析允许对两种物质的可加性、次可加性或协同性进行评估。通过测量运动活动，并使用一定剂量的CART肽和可卡因，单独或一起使用，并采用不同的给药策略，发现了亚可加性的明确证据。CART降低了全身可卡因的运动激活作用，特别是在高剂量的CART下。这些结果表明，vta内CART不仅仅以与可卡因相同的方式起作用，而且可能与可卡因的作用相反。这暗示了CART-DA（多巴胺）相互作用的生理意义和药物开发。(c) 2007 Elsevier Ltd.版权所有。
CART (cocaine- and amphetamine-regulated transcript) peptides appear to be mediators or modulators of psychostimulant drugs. An interesting result in the nucleus accumbens has been that injection of CART peptide has no effect by itself on locomotor activity, but it reduces the locomotor activity induced by cocaine or amphetamine. However, in the ventral tegmental area (VTA), injections of CART peptide have been shown to increase locomotor activity, although to a lesser degree [Kimmel, H.L., Gong, W., Vechia, S.D., Hunter, R.G., Kuhar, M.J., 2000. Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55-102 induces locomotor activity and promotes conditioned place preference. J. Pharmacol. Exp. Ther. 294, 784-792]. This study was carried out to clarify the interaction of intra-VTA CART 55-102 and systemic cocaine on locomotor activity. The CART-cocaine interaction has been examined using the rigorous isobolographic approach. This typo of analysis permits an assessment of additivity, subadditivity, or synergism of two substances. By measuring locomotor activity and using a range of doses of CART peptide and cocaine, both alone and together, with different dosing strategies, clear evidence of subadditivity was found. CART reduced the locomotor activating effects of systemic cocaine, especially at higher doses of CART. These results imply that intra-VTA CART is not simply acting in the same manner as cocaine, and is likely to oppose the action of cocaine. This has implications for the physiological significance of CART-DA (dopamine) interactions and for medications development. (c) 2007 Elsevier Ltd. All rights reserved.