Abstract 2010

Background: Opioids have been shown to acutely inhibit adenylyl cyclase and decrease cAMP levels in the brain. Loss of opioid-inhibited cAMP generation appears to be associated with production of substance P and developmental of tolerance. The purpose of this study was to examine whether cAMP and SP responses to opioids are related to CNS maturity.

Methods: Premature and adult rat brain synaptosomes were isolated and exposed to media with or without MS (100 ng/ml) or M-3-G (100 ng/ml) for 1 and 24 hours. At the end of the incubation period, media samples were collected for measurement of cAMP and SP levels by enzyme immunoassay.

Results: (Values are expressed as mean±SEM). At 1 hour of MS exposure, mean adult synaptosomal cAMP levels increased significantly compared to the control group (129.3±7.0 pmol/ml vs 103.6±2.3 pmol/ml, p<0.05). By 24 hours, MS significantly decreased adult synaptosomal cAMP levels (32.2±5.5 pmol/ml, p<0.001) compared to control levels (68.9±3.6 pmol/ml). M-3-G did not have an effect on adult synaptosomal cAMP at 1 or 24 hours of exposure. Conversely, MS exposure resulted in a significant decrease in premature synaptosomal cAMP levels at 1 hour (50.2±4.4 pmol/ml, p<0.05) compared to control levels (83.5±11.3 pmol/ml). The effect was sustained up to 24 hours of MS exposure (50.2±4.4 pmol/ml, p<0.01) compared to the control group (70.9±7.7), M-3-G did not have an effect on premature synaptosomal cAMP levels at 1 hour, but at 24 hours, the levels dropped to 40.0±3.7 pmol/ml, p<0.01 versus control (70.9±7.7 pmol/ml). Mean adult SP levels did not change among the groups at 1 hour; however, at 24 hours SP levels increased in the MS-treated group (37.2±4.0 pg/ml, p<0.01) compared to the control group (20.1±3.8 pg/ml). Neither MS nor M-3-G had an effect on premature synaptosomal SP levels at 1 or 24 hours of exposure.

Conclusions: These data may suggest that the premature brain has a more sustained response to opioid-induced development of tolerance to opioids.