The effect of LY235959 and rewarding stimulation on intracranial nociception

Abstract

A previous study conducted by Kornetsky et al. (2010) showed that the stimulation of the mesencephalic reticular formation (MRF) along with low intensity stimulation of the medial forebrain (MFB) produces effects that resemble that of an opioid antagonist. Specifically, simultaneous stimulation was found to attenuate the analgesic effects of morphine. It was hypothesized that this phenomenon could be due to the release of an endogenous opioid receptor competitive antagonist (EO RCA) during the simultaneous stimulation of both the reward and nociceptive areas. To investigate this hypothesis, the previous experiment was repeated but substituting morphine with LY235959, a non-opioid analgesic that is a competitive NMDA receptor antagonist. To determine whether the effects of concurrent stimulation pertain only to opioid analgesics, LY235959 was administered along with MRF-MFB stimulation to observe if the analgesic effects of LY235959 could also be reversed by concurrent stimulation. The experimental results of this research show that LY235959 alone exhibits dose-dependent analgesic effects. However, when L Y235959 is administered concurrently with MRF-MFB stimulation, the analgesic effects are reversed, which suggests that concurrent stimulation can reverse the effects of non-opioid analgesic agents. The results of this research thus do not provide sufficient evidence to support the hypothesis that EO RCA was released during simultaneous stimulation. Specifically, the results show that combined stimulation of MRF-MFB has effects that are not limited to the opioid analgesic system.