Adaptations in neurons of the midbrain periaqueductal gray (PAG) induced by chronic morphine treatment mediate expression of many signs of opioid withdrawal. The abnormally elevated action potential rate of opioid-sensitive PAG neurons is a likely cellular mechanism for withdrawal expression. We report here that opioid withdrawal in vitro induced an opioid-sensitive cation current that was mediated by the GABA transporter-1 (GAT-1) and required activation of protein kinase A (PKA) for its expression. Inhibition of GAT-1 or PKA also prevented withdrawal-induced hyperexcitation of PAG neurons. Our findings indicate that GAT-1 currents can directly increase the action potential rates of neurons and that GAT-1 may be a target for therapy to alleviate opioid-withdrawal symptoms.

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The purpose of the present study was to investigate the binding patterns of the plant lectin Bandeiraea simplicifolia I-isolectin B 4 (BSI-B 4 ) to sensory neurones in seven mammalian species. The dorsal root ganglia and spinal cords of three rats, mice, guinea pigs, rabbits, flying foxes, cats, and marmoset monkeys were screened for BSI-B 4 using lectin histochemistry. BSI-B 4 binding was associated with the soma of predominantly smalldiameter primary sensory neurones in the dorsal root ganglia and their axon terminals within laminae I and II of the superficial dorsal horn in all seven species. The similarities of lectin binding patterns in each of these species suggest that the glycoconjugate to which BSI-B 4 binds has a ubiquitous distribution in mammals, and supports the proposal that this lectin may preferentially bind to a subpopulation of sensory neurones with a similar functional role in each of these species. Anat Rec 268: 105-114, 2002.

1. Diving or face immersion bradycardia is a well recognized but incompletely understood reflux which occurs in man and other mammals. 2. In order to investigate the contributions made by voluntary apnoea, face immersion in water and cold exposure, 18 normal subjects were exposed to these challenges separately and in various combination. 3. Tested individually, cold and apnoea caused significant reductions in heart beat (P < 0.01 and 0.002, respectively). Face immersion in thermoneutral water had no effect on heart rate. 4. The bradycardic effect of apnoea at maximal inspiration may be due to stimulation of pulmonary stretch receptors. 5. Cold exposure and voluntary apnoea applied simultaneously caused a summative effect but when tested with face immersion in water there was a synergistic response greater than the sum of individual responses. 6. The results confirm the bradycardic effect of apnoea and cold exposure, whereas immersion in thermoneutral water had little effect, a finding which has been disputed in the literature.

The plant lectin Bandeiraea simplicifolia I-isolectin B4 (BSI-B4) identifies a galactose-containing, membrane-associated glycoconjugate expressed by a discrete subpopulation of unmyelinated primary sensory neurones in the rat. We have previously suggested that BSI-B4 selectively binds to primary sensory neurones that innervate the skin. However, in that study, the tracer diamidino yellow was applied to the cut ends of peripheral nerves to identify neurones innervating particular target tissues. In this study, we have avoided axotomy by retrogradely labelling primary sensory neurones from peripheral tissues using the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbacyanine perchlorate (DiI). DiI was injected into the plantar skin, gastrocnemius muscle, and pyloric region of the stomach in rats. Corresponding ganglia were sectioned, incubated in BSI-B4 conjugated to fluorescein isothiocyanate, and examined with a fluorescence microscope. DiI-labelled cells were identified by red fluorescence within the cytoplasm, whereas cells binding BSI-B4 displayed green fluorescence associated with the plasma membrane and Golgi apparatus. Quantitative analysis revealed that 36.2% of cutaneous neurones, 7.6% of muscle neurones, and 6.8% of visceral neurones expressed the BSI-B4-binding site, indicating that a small but significant proportion of small-diameter primary sensory neurones innervating muscle and viscera also express BSI-B4-binding sites.

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