Opiates are a class of drugs that are used in clinical settings for their analgesic properties, and recreationally for the feelings of euphoria and tranquility they produce. Prolonged and/or frequent exposure to opiates is associated with the appearance of tolerance and dependence, in both the infant and adult human and rodent. In the adult rodent a number of second messenger pathways have been shown to be involved in opiate tolerance and dependence; for instance protein kinase A (PKA) of the CAMP pathway and protein kinase C (PKC) of the IP3 pathway. Very few studies, however focus on how opiate tolerance and dependence are regulated by these pathways in the infant rodent.
The specific aim of the experiments outlined by this grant application is to describe the regulatory role that PKA and PKC play in morphine induced tolerance and dependence in the infant rat. The proposed experiments will be divided into two phases: phase I will investigate the modulation of opiate tolerance and dependence by protein kinases, using common behavioral pharmacology techniques. Phase II will investigate the changes in protein and mRNA levels of PKA and PKC after chronic morphine exposure, using biochemical and neuroanatomical techniques.
| Barr, Gordon A; McPhie-Lalmansingh, Anika; Perez, Jessica et al. (2011) Changing mechanisms of opiate tolerance and withdrawal during early development: animal models of the human experience. ILAR J 52:329-41 |
