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267449 occurrences (No.100 in the rank) during 5 years in the PubMed. [no cache] 500 found

347) To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence.

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PMID:24330252 DOI:10.1111/adb.12120

2015 Addiction biology

* Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence-induced hyperalgesia.

- Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.

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(1)50 magnetic	(18)4 gastrointestinal	(35)3 integration	(52)2 connections
(2)38 connectivity	(19)4 outcome	(36)3 interactions	(53)2 differentiation
(3)29 and	(20)4 outcomes	(37)3 movement	(54)2 domains
(4)8 limitations	(21)4 relationships	(38)3 single	(55)2 endurance
(5)7 network	(22)4 unit	(39)3 status	(56)2 health
(6)7 recovery	(23)3 Assessment	(40)3 status,	(57)2 imaging
(7)7 role	(24)3 MRI	(41)3 studies	(58)2 impact
(8)6 changes	(25)3 Well-Being	(42)2 CD133	(59)2 integrity
(9)6 results	(26)3 activation	(43)2 HL	(60)2 losses
(10)5 alterations	(27)3 brain	(44)2 ability	(61)2 networks
(11)5 limitation	(28)3 consequences	(45)2 activity	(62)2 neuronal
(12)5 neuroimaging	(29)3 coupling	(46)2 analyses	(63)2 organization
(13)5 properties	(30)3 decline	(47)2 as	(64)2 parameters
(14)5 theory	(31)3 deficits	(48)2 assays	(65)2 roles
(15)4 capacity	(32)3 differences	(49)2 assessment	(66)2 significance
(16)4 connectivity,	(33)3 impairment	(50)2 characteristics	(67)2 specialization
(17)4 foods	(34)3 improvement	(51)2 cognitive

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--- WordNet output for functional --- =>機能の, 関数の, 機能する, 機能上の, 実用的な, 機能的な Overview of adj functional The adj functional has 6 senses (first 2 from tagged texts) 1. (3) functional -- (designed for or capable of a particular function or use; "a style of writing in which every word is functional"; "functional architecture") 2. (1) functional -- (involving or affecting function rather than physiology; "functional deafness") 3. functional -- (relating to or based on function especially as opposed to structure; "the problem now is not a constitutional one; it is a functional one"; "delegates elected on a functional rather than a geographical basis") 4. functional, usable, useable, operable, operational -- (fit or ready for use or service; "the toaster was still functional even after being dropped"; "the lawnmower is a bit rusty but still usable"; "an operational aircraft"; "the dishwasher is now in working order") 5. functional -- (designed for or adapted to a function or use; "functional education selects knowledge that is concrete and usable rather than abstract and theoretical"; "functional architecture") 6. running, operative, functional, working -- ((of e.g. a machine) performing or capable of performing; "in running (or working) order"; "a functional set of brakes") --- WordNet end ---