Denervation supersensitivity to serotonin in rat forebrain: single cell studies.
To investigate the development of denervation supersensitivity to serotonin (5-hydroxytryptamine, 5-HT) in the amygdala (AMYG) and the ventral lateral geniculate nucleus (vLGN), single cell recordings, microiontophoretic, histochemical and biochemical techniques were used in the present study. 5-HT projections to the vLGN and the AMYG were destroyed by 5,7-dihydroxytryptamine (5,7-DHT, a relatively selective toxin for 5-HT neurons) injected directly into the lateral ventricle or the ascending 5-HT pathway in the ventromedial tegmentum area. Enhanced responsiveness of cells to the inhibitory effect of microiontophoretically applied 5-HT (ionto-5-HT) began to develop within 24 h and approached a maximum 7 days after 5,7-DHT pretreatment. In general, the time courses for the reduction in both the density of 5-HT fluorescent varicosities and synaptosomal 5-HT uptake activity paralleled the time course for the development of denervation supersensitivity to 5-HT. During the first 2 days after 5,7-DHT, the enhanced sensitivity was selective for 5-HT; responses to D-lysergic acid diethylamide (LSD), norepinephrine (NE) and gamma-aminobutyric acid (GABA) were unchanged. Seven or more days after 5,7-DHT there was a marked increase of the responsiveness of neurons in the vLGN and the AMYG to both 5-HT and LSD (a 5-HT agonist which is not a substrate for the high affinity 5-HT uptake system). At these later times, the responsiveness of cells in the AMYG to NE and to a lesser extent GABA was also increased. In contrast to the marked supersensitivity seen after 5,7-DHT induced denervation, chronic administration of parachlorophenylalanine, a 5-HT synthesis inhibitor, failed to induce 5-HT supersensitivity.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D003714:Denervation; D005829:Geniculate Bodies / Q000187:drug effects*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D008238:Lysergic Acid Diethylamide; D009638:Norepinephrine