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Spinal effects of the calmodulin inhibitor calmidazolium on dorsal horn neurons in the rat

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Menendez L., Baamonde A., Hidalgo A.

Acta Neurobiologiae Experimentalis

1999

vol. 59

issue 1

31-35

Drugs able to inhibit calmodulin activation can prevent some consequences of the rise in intracellular calcium. It has recently been shown that intrathecal injection of calmodulin inhibitors induce analgesia in rats. We study here the effect induced by the calmodulin inhibitor, calmidazolium, on the activity of dorsal horn neurons driven by noxious and non-noxious stimuli. Extracellular recordings of convergent (n = 12), low-threshold mechanoreceptive (n = 5) and proprioceptive (n = 5) units were made in the presence of calmidazolium. Calmidazolium (600 mg) reduced the noxious (50oC) heat-evoked responses obtained in convergent neurons. On the contrary, the non-noxious tactile responses obtained in low-threshold mechanoreceptive neurons as well as the joint movement-evoked responses obtained in proprioceptive units remained unmodified. We conclude that calmidazolium can block nociceptive processing in the spinal cord and that this fact can help to explain the analgesic effects that intrathecal W-7 and calmidazolium induce in behavioral tests.

Effects of DAGO on the rodent hippocampal evoked potentials using different perfusion solutions

88%

San_ M. S., Menendez L., Gutierrez M., Hidalgo A., Baamonde A.

Opioid receptor agonists exert excitatory effects in the hippocampus by inhibiting GABA release. We report that the mu-opioid agonist, DAGO, increases the amplitude of the population spikes (PS) measured in the stratum pyramidale of the CA1 cell layer in mouse and rat hippocampal slices perfused with an artificial cerebrospinal fluid (ACSF), but not when perfused in Krebs solution. The GABA A agonist, 3-APS, induces inhibitory responses when perfused in either ACSF or Krebs. Also, the field excitatory postsynaptic potentials (EPSP) measured on stratum radiatum do not differ when the slice is perfused with either ACSF or Krebs. The increase in the amplitude of the PS induced by DAGO is not obtained when perfused in a modified ACSF whose concentration of MgSO4 was lowered to its concentration in the Krebs solution (from 2.4 mM to 1.2 mM). Thus, changes in the concentration of MgSO4 seem to be responsible for the different responses induced by DAGO.

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2 Acta Neurobiologiae Experimentalis

1 2000

1 1999

2 Baamonde A.

2 Hidalgo A.

2 Menendez L.

1 Gutierrez M.

1 San_ M. S.

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Spinal effects of the calmodulin inhibitor calmidazolium on dorsal horn neurons in the rat

Effects of DAGO on the rodent hippocampal evoked potentials using different perfusion solutions