Dorsomedial hypothalamic GABA dysfunction produces physiological arousal following sodium lactate infusions

Anantha Shekhar, S. R. Keim, J. R. Simon, W. J. McBride

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Since impairing gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition in the dorsomedial hypothalamus (DMH) of rats elicits a panic-like response, experiments were conducted to test if rats with GABA dysfunction in the DMH would be vulnerable to precipitation of a panic-like response after intravenous sodium lactate infusions. Rats were implanted with unilateral infusion cannula into the DMH which were connected with Alzet minipumps that chronically infused (3.5 nmol/μl/h) either a-CSF (vehicle), dl-(racemic), l-(active) or d-(inactive) isomers of allylglycine (AG), an inhibitor of GABA synthesis. Another group of rats had l-allylglycine pumps implanted in the paraventricular nucleus of the hypothalamus (PVN) as anatomical controls. Animals were tested in the social interaction (SI) test and given sodium lactate infusions (10 ml/kg/15 min) before Alzet pump implantations and on days 4, 7, and 14 after pump placement. Rats were also tested in the elevated plus-maze on treatment day 4. Chronic impairment of GABA function in the DMH and not PVN resulted in rats being more anxious in the SI test on treatment days 4, 7, and 14 and in the elevated plus-maze on day 4 compared to a-CSF and d-AG infusions. Further, rats with GABA dysfunction in the DMH, and not PVN, exhibited significant increases in heart rate and blood pressure following IV sodium lactate infusions. There were significant decreases in DMH glutamic acid decarboxylase activity and GABA content in rats receiving 7 days of dl-AG or l-AG infusions. These results indicate that chronic reduction of GABA function in the DMH leads to the development of panic-like disorder in this animal model.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume55
Issue number2
DOIs
StatePublished - Oct 1996

Fingerprint

Sodium Lactate
Allylglycine
Arousal
gamma-Aminobutyric Acid
Hypothalamus
Rats
Paraventricular Hypothalamic Nucleus
Pumps
Panic
Interpersonal Relations
Animals
Glutamate Decarboxylase
Blood pressure
GABA Receptors
Isomers
Panic Disorder
Animal Models
Heart Rate

Keywords

  • Alzet pumps
  • Anxiety
  • Dorsomedial hypothalamus
  • Lactate infusion
  • Panic disorder
  • Social interaction elevated plus-maze

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Dorsomedial hypothalamic GABA dysfunction produces physiological arousal following sodium lactate infusions. / Shekhar, Anantha; Keim, S. R.; Simon, J. R.; McBride, W. J.

In: Pharmacology Biochemistry and Behavior, Vol. 55, No. 2, 10.1996, p. 249-256.

Research output: Contribution to journalArticle

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