Neuropharmacology
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Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory and its cellular model, i.e. hippocampal long-term potentiation (LTP) in CA1. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (late-LTP) by activating the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors (Frey, 2001, Long-lasting hippocampal plasticity: cellular model for memory consolidation? In: Richter, D. (Ed.), Cell Polarity and Subcellular RNA Localization. ⋯ The question arises as to whether D1/D5-LTP also requires glutamatergic stimulation, i.e. NMDA-receptor activation. We provide first evidence that a synergistic role of D1/D5- as well as NMDA-receptor-function is required in mediating processes relevant for the maintenance of this protein synthesis-dependent potentiation.
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The alpha(2)-adrenoceptors (alpha(2)-ARs) are located on primary afferent terminals and on neurons in the spinal cord dorsal horn. However, their relative contribution to the analgesic effect of the alpha(2)-AR agonists is not known. In this study, we determined the role of certain presynaptic alpha(2)-ARs in the antinociceptive effect produced by intrathecal administration of the alpha(2)-AR agonist clonidine. ⋯ Furthermore, in the vehicle-treated group, although intrathecal injection of clonidine produced a large increase in the thermal withdrawal latency, it only had a small and short-lasting effect on the mechanical withdrawal threshold. This study provides new information that the antinociceptive effect of spinally administered alpha(2)-AR agonists is largely modality-specific. Loss of TRPV1-expressing sensory neurons leads to a reduction in presynaptic alpha(2A)-ARs but paradoxically potentiates the effect of clonidine on mechano-nociception.