title: Altered neuronal responsiveness to biogenic amines in rat cerebral cortex after serotonin denervation or depletion.
abstract: To further investigate monoaminergic mechanisms in cerebral cortex, responsiveness of cortical neurons to microiontophoretic applications of serotonin (5-HT), dopamine (DA) or noradrenaline (NA) was examined in the frontoparietal region of control, 5,7-dihydroxytryptamine (5,7-DHT)- and p-chlorophenylalanine (PCPA)-treated rats anesthetized with urethane. As a rule, 100 nA applications of either one of these biogenic amines induced marked slowing or total interruption of 'spontaneous' firing overlasting the 30 s period of ejection. Given the large amounts of monoamines ejected, it could be inferred that such microiontophoretic applications produced a maximal activation of receptors. In control rats, the responses to 5-HT, DA and NA were of approximately equal duration (approximately equal to 5 min). Two to 4 weeks after denervation with 5,7-DHT, most neurons (75%) exhibited greatly prolonged responses to 5-HT (approximately equal to 14 min), and marked depressions of firing could be induced by small ejection currents (approximately equal to 2 nA) having little or no effect in the controls. In addition, 85% of the units supersensitive to 5-HT showed considerably shortened responses to DA and NA (approximately equal to 1 min). After 2-14 days of depletion with PCPA, there was no change in the responsiveness to 5-HT in spite of a 91% lowering of cortical 5-HT content equivalent to that measured after denervation. Nevertheless, responsiveness to DA and NA was again diminished in a majority (80%) of the units tested. In control or PCPA-treated rats, acute administration of the 5-HT re-uptake blocker fluoxetine increased the duration of depressions induced by 100 nA applications of 5-HT but did not enhance responsiveness to low ejection currents. This suggested that, after 5-HT denervation, the suppression of re-uptake was mainly responsible for the prolongation of 5-HT responses ('presynaptic' component of supersensitivity), whereas a modification of 5-HT receptors accounted for the greater efficacy of small doses of 5-HT ('postsynaptic' component). Responsiveness to the microiontophoretic application of phenylephrine (PHE), a noradrenergic a-agonist, was comparable with that to NA in PCPA- and 5,7-DHT-treated as well as in control rats. Therefore, the hyposensitivity to DA and NA appeared indicative of a desensitization of catecholamine receptors caused by the absence of 5-HT. Such a desensitization may be viewed as an adaptive change resulting from an increased release of endogenous DA and NA. This interpretation would in turn imply that, normally, 5-HT regulates catecholamine release in the neocortex.
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D005071:Evoked Potentials; D008297:Male; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine