Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, C9



Poole,Sarah Louise; Deuchars,Susan ; Lewis,David ;

1. Biomedical Science, University of Leeds, Leeds, West Yorkshire, United Kingdom.

There are three major subtypes of opioid receptor, mu (μ), kappa(κ) and delta (δ), located in various CNS regions. The mu-opioid receptor (MOR) has been shown experimentally to have the most potent effects in relation to cardiovascular and gastrointestinal functions. Microinjection of the MOR agonist, DAMGO, into the NTS significantly increased food intake, kappa and delta opioid agonists were without effect (Kotz et al.1997). At the cellular level, DAMGO has pre- and postsynaptic effects on neurones within the NTS, inducing a hyperpolarisation of the membrane and a decrease in evoked EPSP amplitude (Rhim et al.1993). The specific location of DAMGO responsive neurones was not determined, which is pertinent since immunohistochemical studies have demonstrated intense staining for the MOR within the commissural and the dorsal medial subnucleus of the NTS, with only moderate staining of the lateral and ventral medial subdivisions (Nomura et al. 1996). Since these receptors could be located either pre- or post-synaptically, the aim of these studies was to evaluate the region specificity, within the NTS, of pre- and post-synaptic responses to DAMGO. Male Wistar rats (18 day) were humanely killed by anaesthetising with Sagatal (60mg/Kg i.p.), coronal medullary slices (300μm) prepared and whole cell patch clamp recordings made from visually identified NTS neurones using electrodes containing Lucifer yellow for post-recording localisation of the neurones (Bouryi & Lewis, 2003). To evoke synaptic potentials, a stimulating electrode was placed in the solitary tract. DAMGO (100nM) elicited a membrane hyperpolarisation of 6.9±0.91mV (mean±S.E.M.) and a decrease in input resistance (305.6±61.8MΩ) in 11 out of 22 medial neurones with 6 commissural, 2 ventral medial, 1 dorsal, 1 ventral and 7 intermediate neurones being unresponsive. DAMGO also decreased the peak amplitudes of pairs of EPSPs,(61±6.8% decrease 1st EPSP; and 46 ±7.9% decrease 2nd EPSP), resulting in an increase in the paired pulse ratio from 0.632±0.05 to 0.981±0.13 (P<0.01, paired t test, n=10). These presynaptic effects were blocked by the MOR antagonist CTOP (1μM) Neurones responsive to the presynaptic actions of DAMGO were located throughout the NTS. These data suggest that whilst the presynaptic actions of DAMGO are ubiquitous throughout the NTS, postsynaptic responses are restricted to specific subdivisions of the nucleus. It may be that these neurones have specific roles in autonomic function.

Where applicable, experiments conform with Society ethical requirements