Cross-tolerance between two brainstem sites supporting stimulation-produced analgesia.

Male albino Holtzman rats were stereotaxically implanted with two bipolar stimulating electrodes, aimed at the periaqueductal gray matter of the brainstem. Focal brain stimulation-produced analgesia was assessed by the tail-flick method. After establishing that focal brain stimulation elicited analgesia at both sites, behavioral tolerance (i.e., reduced analgesia) was induced at one site through repeated stimulation. Upon elicitation of tolerance at one site, stimulation was immediately switched to the other site (which had not been previously rendered tolerant) and analgesia was assessed. Tail-flick latencies revealed transfer of behavioral tolerance from the site given repeated stimulation to the site not given repeated stimulation. While the mechanism involved in this cross-tolerance is not known, a neurochemical substrate may be involved.