Monoaminergic denervation of the rat hippocampus: microiontophoretic studies on pre- and postsynaptic supersensitivity to norepinephrine and serotonin.
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.
D000818:Animals; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006892:Hydroxydopamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D004102:Dihydroxytryptamines; D006892:Hydroxydopamines; D005473:Fluoxetine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D007545:Isoproterenol; D003891:Desipramine; D009638:Norepinephrine