Development of acute opioid tolerance and dependence in rat striatal neurones

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Abstract
Striatal neurones in the rat were frequently observed to develop tachyphylaxis to the specific, naloxone-antagonisable depressant effects of methionine-and leucine-enkephalin on spontaneous and L-glutamate-evoked activity. This loss of responsiveness to the enkephalins occurred within a few minutes of the repeated or prolonged application of these peptides and is suggested to reflect a form of acute tolerance. As with chronic opiate tolerance, the acute tolerance of single striatal neurones to the enkephalins appeared to be associated with dependence on these opioids, as evinced by the withdrawal-like hyperactivity that occurred upon terminating the application of the peptides or upon the microelectrophoresis of naloxone.