Effect of amygdala kindling on the in vivo release of GABA and 5-HT in the dorsal raphe nucleus in freely moving rats.
Our laboratory has previously reported a significant subsensitivity to iontophoretically applied GABA (gamma-aminobutyric acid) in dorsal raphe neurons of amygdala-kindled rats. This subsensitivity was selective for GABA and persisted at least 3 months after the last kindled seizure. In the present series of experiments, we explored mechanisms by which kindling could result in persistent GABA sensitivity changes, using in vivo microdialysis to quantitate neurotransmitter [including GABA and 5-hydroxytryptamine (5-HT)] release in the dorsal raphe nucleus of awake, unrestrained amygdala-kindled rats. Depolarization-induced release of GABA is markedly increased in the dorsal raphe nucleus in amygdala-kindled animals. This change in depolarization-induced GABA release appeared to be graded, dependent upon the stage to which the animal is kindled. Thus GABA release is increased in animals kindled to Stage 2 and even greater in animals kindled to Stage 5 seizures. The change in GABA release is also selective, since no consistent change in the release of other putative amino acid neurotransmitters or 5-HT was observed in these same animals. We hypothesize that this increase in depolarization-induced release of GABA in the amygdala-kindled animal underlies the development of subsensitivity to GABA in dorsal raphe neurons.
During
M J
MJ
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510.
Craig
J S
JS
Hernandez
T D
TD
Anderson
G M
GM
Gallager
D W
DW
D000596:Amino Acids / Q000378:metabolism; D000679:Amygdala / Q000033:anatomy & histology / Q000502:physiology*; D000818:Animals; D003956:Dialysis; D005473:Fluoxetine / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D009557:Nipecotic Acids; D005473:Fluoxetine; C030278:nipecotic acid; D012701:Serotonin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D011392:Proline; C010983:homoproline; D011188:Potassium