Monoaminergic denervation of the rat hippocampus: microiontophoretic studies on pre- and postsynaptic supersensitivity to norepinephrine and serotonin

Brain Res. 1980 Nov 3;200(2):363-76. doi: 10.1016/0006-8993(80)90927-0.

Abstract

The responsiveness of hippocampal CA3 pyramidal neurons to microiontophoretic applications of serotonin (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA) and isoproterenol (ISO) was assessed in rats following 5,7-dihydroxy-tryptamine (5,7-DHT) and 6-hydroxydopamine (6-OHDA) pretreatments and bilateral locus coeruleus lesions. The intraventricular administration of 200 micrograms (free base) of 5,7-DHT and of 6-OHDA produced 89% and 93% decreases of 5-HT and NE respectively. None of these pretreatments modified the inital responsiveness to, or recovery from iontophoretic application of 5-HT. In 6-OHDA pretreated and locus-lesioned rats, the initial effectiveness of NE was not altered but its effect was markedly prolonged. However, there was no such prolongation of the effect of ISO which is not a substrate for the high affinity NE reuptake. The effect of GABA was not affected by these pretreatments. Acute pharmacological blockade of the NE reuptake with desipramine (5 mg/kg, i.p.) similarly induced a prolongation of the effect of iontophoretically applied NE, while fluoxetine (10 mg/kg, i.p.) a 5-HT reuptake blocker, failed to alter the recovery of pyramidal cells from iontophoretic application of 5-HT. It is concluded that 5-HT denervation induces neither pre- nor postsynaptic types of supersensitivity in hippocampal pyramidal cells, contrasting with the previously shown supersensitivity of ventral lateral geniculate and amygdaloid neurons following 5-HT denervation. NE denervation fails to induce a postsynaptic type of supersensitivity but leads to a marked prolongation of the response to NE indicative of a presynaptic mechanism. These results underscore the necessity for regional studies of neurotransmitters and drug action.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Denervation*
  • Desipramine / pharmacology
  • Dihydroxytryptamines / pharmacology
  • Fluoxetine / pharmacology
  • Hippocampus* / drug effects
  • Hippocampus* / physiology*
  • Hydroxydopamines / pharmacology
  • Isoproterenol / pharmacology
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / physiology
  • Male
  • Norepinephrine / pharmacology*
  • Rats
  • Serotonin / pharmacology*
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Dihydroxytryptamines
  • Hydroxydopamines
  • Fluoxetine
  • Serotonin
  • gamma-Aminobutyric Acid
  • Isoproterenol
  • Desipramine
  • Norepinephrine