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Effects of ZK 93426 on muscarinic and nicotinic antagonist or nucleus basalis lesioning-induced electrocortical slowing

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The present study investigated the effects of a benzodiazepine receptor antagonist, β-carboline ZK 93426 (1, 3 and 10 mg/kg, IP), on scopolamine and nucleus basalis (NB) quisqualic acid lesion-induced neocortical electrocortical activity slowing in rats. Scopolamine induced a dose dependent increase in EEG spectral values and slow delta waves (0.3<0.9=2.7 mg/kg IP). ZK 93426 partially reversed EEG slowing induced by the smallest scopolamine dose (0.3 mg/kg), but had no effect on the EEG changes induced by higher doses. A combination of scopolamine at 0.3 mg/kg and mecamylamine (a centrally active nicotinic antagonist) at 10 mg/kg induced an EEG slowing that was not reversed by ZK 93426. NB lesions markedly decreased cortical choline acetyltransferase (ChAT) activity (−77%) and increased EEG slow waves. ZK 93426 had no effect on the NB lesion-induced slow wave activity increase. The present results support the idea that β-carboline ZK 93426 may increase cortical cholinergic activity by disinhibiting the NB cholinergic neurons. However, if the activity of “NB to cortex” cholinergic system is greatly decreased by either a marked reduction in NB cell number (in NB-lesioned rats), a near complete cortical post-synaptic muscarinic receptor blockade (large scopolamine dose) or by a combination of nicotinic (decrease acetylcholine release) and muscarinic receptor blockade, the effects of β-carboline ZK 93426 on EEG slowing may be negligible.

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Correspondence to Paavo Riekkinen Jr.

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Riekkinen, P., Riekkinen, M., Sirviö, J. et al. Effects of ZK 93426 on muscarinic and nicotinic antagonist or nucleus basalis lesioning-induced electrocortical slowing. Psychopharmacology 111, 195–201 (1993).

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Key words

  • β-Carboline ZK 93426
  • Scopolamine
  • Mecamylamine
  • Nucleus basalis
  • Disinhibition
  • Neocortical EEG slowing