THE EFFECTS OF SELECTIVE OPIOID ANTAGONISTS ON SOMATOSENSORY-EVOKED POTENTIALS DURING RELATIVE CEREBRAL-ISCHEMIA IN RATS

Hemorrhagic hypotension in spontaneously hypertensive rats induces att enuation of somatosensory evoked potentials. In this model of relative ly mild cerebral ischemia, our previous studies have shown that naloxo ne stereospecifically enhances the evoked potentials, without changes in cortical blood flow. The high dose of naloxone needed to enhance th e evoked potentials suggests that the attenuation is mediated by low a ffinity opioid receptors (delta or kappa). In the present study, we us ed this model to study the effects of naloxone-methobromide (5 mg kg(- 1), a quaternary derivative of naloxone with selective peripheral acti on when injected intravenousely), MR 2266 (1 mg kg(-1), a kappa recept or antagonist), and naloxone (5 mg kg(-1)) as well as saline injection (as control) in four different groups of rats. Following injection, w e examined the changes in somatosensory evoked potentials, cortical bl ood flow and heart rate for 15 min while mean arterial pressure was he ld constant by a pressure-regulating reservoir. Only naloxone changed the somatosensory evoked potential amplitude significantly compared wi th the saline group in which no effect was seen. However, there was a tendency for a delayed effect of naloxone-methobromide on the evoked p otentials, possibly indicating that the substance slowly passes the bl ood-brain barrier. Naloxone and MR 2266 caused a transient decrease in heart rate, while following naloxone-methobromide injection there was a slight increase in heart rate. Our results thus indicate that the b eneficial effects of naloxone on somatosensory evoked potentials durin g relative cerebral ischemia may be centrally mediated by a non-kappa mechanism.