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147) 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.
- 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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Overview of noun effects
The noun effects has 1 sense (no senses from tagged texts)
1. effects, personal effects -- (property of a personal character that is portable but not used in
business; "she left some of her personal effects in the house"; "I watched over their effects until
they returned")
Overview of noun effect
The noun effect has 6 senses (first 5 from tagged texts)
1. (101) consequence, effect, outcome, result, event, issue, upshot -- (a phenomenon that follows
and is caused by some previous phenomenon; "the magnetic effect was greater when the rod was
lengthwise"; "his decision had depressing consequences for business"; "he acted very wise after the
event")
2. (11) impression, effect -- (an outward appearance; "he made a good impression"; "I wanted to
create an impression of success"; "she retained that bold effect in her reproductions of the
original painting")
3. (9) effect -- (an impression (especially one that is artificial or contrived); "he just did it
for effect")
4. (2) effect, essence, burden, core, gist -- (the central meaning or theme of a speech or literary
work)
5. (1) effect, force -- ((of a law) having legal validity; "the law is still in effect")
6. effect -- (a symptom caused by an illness or a drug; "the effects of sleep loss"; "the effect of
the anesthetic")
Overview of verb effect
The verb effect has 2 senses (first 2 from tagged texts)
1. (17) effect, effectuate, set up -- (produce; "The scientists set up a shock wave")
2. (3) effect -- (act so as to bring into existence; "effect a change")
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