Disruption of GABAergic tone in the dorsomedial hypothalamus attenuates responses in a subset of serotonergic neurons in the dorsal raphe nucleus following lactate-induced panic.
Panic patients are vulnerable to induction of panic attacks by sub-threshold interoceptive stimuli such as intravenous (i.v.) sodium lactate infusions. Facilitation of serotonergic signaling with selective serotonin reuptake inhibitors can suppress anxiety and panic-like responses, but the mechanisms involved are not clearly defined. We investigated the effects of i.v. 0.5 M sodium lactate or saline, in control and panic-prone rats on c-Fos expression in serotonergic neurons within subdivisions of the midbrain/pontine raphe nuclei. Rats were chronically infused with either the GABA synthesis inhibitor l-allylglycine into the dorsomedial hypo thalamus to make them panic-prone, or the enantiomer d-allylglycine (d-AG) in controls. Lactate increased c-Fos expression in serotonergic neurons located in the ventrolateral part of the dorsal raphe nucleus (DRVL) and ventrolateral periaqueductal gray (VLPAG) of control, but not panic-prone, rats. The distribution of lactate-sensitive serotonergic neurons in d-AG-treated rats is virtually identical to previously defined pre-sympathomotor serotonergic neurons with multisynaptic projections to peripheral organs mediating 'fight-or-flight'-related autonomic and motor responses. We hypothesized that serotonergic neurons within the DRVL/VLPAG region represent a 'sympathomotor control system' that normally limits autonomic/behavioral responses to innocuous interoceptive and exteroceptive stimuli, and that dysfunction of this serotonergic system contributes to an anxiety-like state and increases vulnerability to panic in animals and humans.
Johnson
Pl
P
Department of Psychiatry and Biochemistry, Indiana University School of Medicine, Indianapolis, IN 46223, USA.
Lowry
Ca
C
Truitt
W
W
Shekhar
A
A
D000501:Allylglycine / Q000494:pharmacology; D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000502:physiology*; D016584:Panic Disorder / Q000139:chemically induced / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D019354:Sodium Lactate / Q000009:adverse effects / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D000501:Allylglycine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D019354:Sodium Lactate