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Exp Brain Res (2011) 212:517528 DOI 10.1007/s00221-011-2759-z
RESEARCH ARTICLE
Apamin increases post-spike excitability of supraoptic nucleus neurons in anaesthetized morphine-nave ratsand morphine-dependent rats: consequencesfor morphine withdrawal excitation
Philip M. Bull John A. Russell Victoria Scott
Colin H. Brown
Received: 14 January 2011 / Accepted: 31 May 2011 / Published online: 14 June 2011 Springer-Verlag 2011
Abstract Supraoptic nucleus (SON) oxytocin neurons develop morphine dependence when chronically exposed to this opiate and undergo excitation when morphine is subsequently withdrawn. Morphine withdrawal excitation is evident as an increased action potential (spike) ring rate and is associated with an increased post-spike excitability that is consistent with the expression of an enhanced post-spike afterdepolarization (ADP) during withdrawal. Here, we administered apamin (which inhibits the medium after-hyperpolarization [mAHP] in vitro and unmasks an ADP) into the SON of urethane-anaesthetized rats to determine its effects on oxytocin neurons in vivo. As predicted, intra-SON apamin administration increased the propensity to re a spike soon (\100 ms) after each spike (post-spike excitability) more in oxytocin neurons recorded from morphine-treated rats than in morphine-nave rats. However, intra-SON apamin did not alter the overall ring rate of oxytocin neurons recorded from morphine-treated rats or morphine-nave rats, indicating that an increase in post-spike excitability alone is not sufcient to trigger withdrawal excitation of oxytocin neurons. Nevertheless, bilateral intra-SON apamin infusion increased oxytocin secretion (which depends on ring pattern as well as ring rate) by 90 46% in morphine-dependent rats (P \ 0.01 compared to aCSF).
Hence, an increase in post-spike excitability does not appear to drive morphine withdrawal-induced increases in oxytocin
neuron ring rate, but does contribute to withdrawal-induced hyper-secretion of oxytocin.
Keywords Apamin Intrinsic excitability Naloxone
Opioid Oxytocin Vasopressin
Introduction
Morphine and heroin are used clinically in pain management. However, these opiate analgesics are subject to widespread abuse that can result in dependence and addiction. Whereas abuse of opiates is facilitated by their euphoric actions, a major factor in moving from abuse to addiction is the avoidance of the debilitating withdrawal symptoms that occur when drug use is stopped (Kenny et al. 2006). At present, the cellular processes that induce dependence and underpin the withdrawal syndrome are poorly understood.
Morphine and heroin are agonists of l-opioid receptors, which are widely expressed in the central nervous...