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Separating analgesia from reward within the ventral tegmental area
E Schifirneţ1, S E Bowen1, G S Borszcz1
1Behavioral and Cognitive Neuroscience Program, Department of Psychology, Wayne State University, Detroit, MI 48202, USA.
Neuroscience
|January 18, 2014
Summary
Cholinergic agonists in the ventral tegmental area (VTA) reduce pain responses and create reward. Different receptors in VTA subregions mediate analgesia and reward, suggesting potential to separate these effects for addiction treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- The mesolimbic reward circuit, originating in the ventral tegmental area (VTA), is implicated in pain modulation and addiction.
- Cholinergic activation of VTA dopamine neurons is known to be rewarding and may suppress pain responses.
Purpose of the Study:
- To investigate regional differences within the VTA regarding the effects of carbachol on affective analgesia and reward.
- To determine the specific roles of muscarinic and nicotinic receptors in these VTA-mediated effects.
Main Methods:
- Rats received unilateral injections of carbachol (cholinergic agonist) into anterior (aVTA), mid, or posterior (pVTA) VTA.
- Affective pain response was measured by vocalization afterdischarges (VADs).
- Reward was assessed using conditioned place preference (CPP) learning, with antagonists (atropine for muscarinic, mecamylamine for nicotinic) administered to assess receptor involvement.
Main Results:
- Carbachol injections into aVTA and pVTA suppressed VADs and supported CPP; midVTA injections had no effect.
- Both nicotinic and muscarinic receptors contributed to carbachol-induced analgesia in aVTA.
- Only muscarinic receptors mediated carbachol analgesia in pVTA, while both receptor types mediated reward in both regions.
- Nicotinic antagonism in pVTA blocked reward but not analgesia.
Conclusions:
- Neural substrates for affective analgesia and reward overlap within the VTA but are not identical.
- Distinct cholinergic mechanisms mediate analgesia and reward in the posterior VTA (pVTA).
- Findings suggest that the rewarding properties of analgesics, linked to addiction liability, can be neuropharmacologically separated from their analgesic effects in the pVTA.
