Related Experiment Videos
Selective alterations of opiate receptor subtypes in monosodium glutamate-treated rats
Abstract:
Neonatal treatment of rats with monosodium glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta-endorphin (B-END) system. The effects on opiate receptors of the loss of B-END is unknown. Neonatal rats were treated with MSG as previously described. After reaching maturity (7-9 months), MSG-treated rats and litter-matched untreated control rats were decapitated and brains dissected into brain regions. Opiate receptor assays were run with [3H]morphine (mu receptor ligand) and [3H]D-alanine2-D-leucine5 (DADL) enkephalin (delta receptor ligand) for each brain region for both MSG and control rats simultaneously. Scatchard plot analyses showed a selective increase in delta receptors in the thalamus only. No corresponding change in mu receptors in the thalamus was found. The cross-competition IC50 data supported this conclusion, showing a loss in the potency of morphine in displacing [3H]DADL enkephalin in the thalamus of MSG-treated rats. This shift in delta receptors produced an IC50 displacement pattern in thalamus, ordinarily a mu-rich area, similar to that of striatum or cortex, delta-rich areas, again indicating an increase in delta receptors. Similar changes in delta receptors in other brain regions were not found. These results represent one of the few examples of a selective and localized shift in delta with no change in mu sites. Furthermore, the delta increase may reflect an up-regulation of the receptors in thalamus after chronic loss of the endogenous opioid B-END.
Insights
Neonatal monosodium glutamate (MSG) treatment in rats selectively increased delta opiate receptors in the thalamus. This localized shift occurred without altering mu receptors, potentially reflecting an upregulation due to lost beta-endorphin (B-END).
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Neonatal monosodium glutamate (MSG) administration destroys arcuate nucleus neurons, including the beta-endorphin (B-END) system.
- The impact of B-END depletion on opiate receptor expression remains largely unknown.
Purpose of the Study:
- To investigate the effects of neonatal MSG-induced B-END loss on mu and delta opiate receptor populations in mature rat brains.
- To determine if the loss of endogenous B-END leads to compensatory changes in opiate receptor density or affinity.
Main Methods:
- Neonatal rats were treated with MSG or served as controls.
- At maturity (7-9 months), brains were dissected into regions.
- Opiate receptor assays using [3H]morphine (mu) and [3H]DADL enkephalin (delta) ligands were performed on brain homogenates.
- Scatchard plot and cross-competition IC50 analyses were conducted.
Main Results:
- A selective and significant increase in delta opiate receptors was observed exclusively in the thalamus of MSG-treated rats.
- No changes in mu opiate receptors were detected in the thalamus.
- Cross-competition data indicated a reduced potency of morphine in displacing delta ligands in the thalamus of MSG-treated rats, consistent with increased delta receptor expression.
- Similar alterations in delta receptor levels were not found in other brain regions examined.
Conclusions:
- Neonatal MSG treatment induces a localized upregulation of delta opiate receptors in the thalamus.
- This phenomenon may represent a compensatory mechanism for the chronic absence of endogenous beta-endorphin (B-END).
- These findings provide a rare example of a selective, regional shift in opiate receptor subtypes.