The Effect of Agents Acting on NMDA and Dopamine Receptors on the Responses of Phrenic Nerve-Diaphram Preparations from Aged Rats
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- Category: Vol. 77, June 2009
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The Effect of Agents Acting on NMDA and Dopamine Receptors on the Responses of Phrenic Nerve-Diaphram Preparations from Aged Rats,SOHA A. EL-MOURSY, HEBA M. SHAWKY, ZAINAB ABDEL WAHAB and LAILA RASHED
Abstract
Background/Aims: Alzheimer’s Dementia (AD) and Par-kinsonism are common in geriatric patients. The skeletal muscles are important in the proper function of aging animals and humans. This study focuses on the influence of memantine (used for moderate to severe AD) and levodopa/carbidopa (LD/CD) (a corner stone in the treatment of Parkinsonism) on responses of isolated phrenic nerve-diaphragms (IPNDs) of aged male rats.
Methods: From 100 aged male albino rats twenty were un-treated to study in vitro effects of memantine and LD/CD on IPNDs. Eighty rats were divided into: Group-I (Control), Group-II (oral memantine, 1.5mg/Kg/d), Group-III, (twice daily intra-peritoneal LD/CD, 25/2.5mg/kg), Group-IV (both drugs). After three weeks of treatment, animals were sacrificed; ten rats from each group were used to harvest IPNDs to study the effect of gallamine; 10 rats were used to measure nAchR (nicotinic acetylcholine receptor) alpha subunit mRNA by PCR.
Results: Heights of indirectly elicited contractions: 63.1± 4.6, 41.5±4.5, 70.6±4.7, 53.9±3.3mm for Groups I through IV respectively, all differences were statistically significant (p<0.05). Memantine treatment caused a leftward shift of gallamine log-concentration-response curve, LD/CD caused rightward shift. Reversal of neuromuscular block required larger neostigmine concentrations in the memantine group and smaller concentrations in the LD/CD group. In vitro memantine inhibited diaphragmatic responses to indirect stimulation. Values of nAchR alpha subunit mRNA (mg/dl): 0.7±0.16 (control), 0.13±0.11 (memnatine), 2.3±0.94 (LD/CD), 1.18±0.71 (both drugs) (p<0.05).
Conclusion: Memnatine inhibits neuromuscular transmis-sion in vitro and with in vivo treatment. LD/CD treatment enhances neuromuscular transmission. Clinical implications need further investigation.