Posted by medievil on December 11, 2006, at 11:02:08
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by medievil on December 11, 2006, at 0:13:24
allright, CCK doesnt seem to be responsible for the tolerance to serotonin, NK receptors do!
now i'm up to find what causes tolerance to GABASustained blockade of neurokinin-1 receptors
enhances serotonin neurotransmissionBACKGROUND: Antagonists of neurokinin-1 (NK(1)) receptors, through which substance P acts, have been proposed to belong to a new class of antidepressants with a unique mode of action. It was postulated that they exert this putative therapeutic effect independently of the serotonin (5-HT) neurons. METHODS: The aim of the present study was to assess, using in vivo electrophysiological paradigms, the effects of sustained administration of the nonpeptidic NK(1) antagonist CP-96,345 on the firing activity of rat dorsal raphe 5-HT neurons, the responsiveness of pre- and postsynaptic 5-HT(1A) receptors, and overall 5-HT neurotransmission in the hippocampus. RESULTS: Both short- and long-term treatments with CP-96,345 significantly increased the spontaneous firing activity of dorsal raphe 5-HT neurons, and this increase was associated with an attenuation of somatodendritic 5-HT(1A) autoreceptor responsiveness. In contrast, the inactive enantiomer of CP-96,345 at NK(1) receptors, CP-96,344, did not alter these parameters after short-term administration. Because 5-HT(1A) receptor activation inhibits the firing activity of dorsal hippocampus CA(3) pyramidal neurons, the degree of disinhibition produced by the selective 5-HT(1A) receptor antagonist WAY 100635 was determined to assess the net change in 5-HT neurotransmission. Intravenous injection of WAY 100635 did not disinhibit CA(3) pyramidal neuron firing in rats given saline, CP-96,345 for 2 days, or CP-96,344 for 14 days, but produced a significant enhancement of firing in rats treated with CP-96,345 for 2 weeks. Therefore, only long-term treatment with CP-96,345 enhanced the tonic activation of postsynaptic 5-HT(1A) receptors. CONCLUSIONS: Similar to all other major types of antidepressant treatments, these data indicate that substance P antagonists might alleviate anxiety and major depression, at least in part, by enhancing the degree of activation of some 5-HT receptors in the forebrain.
poster:medievil
thread:712111
URL: http://www.dr-bob.org/babble/20061206/msgs/712555.html