The circumventricular organs form a potential neural pathway for lactate sensitivity: implications for panic disorder

Area of Science:

• Neuroscience
• Psychiatry
• Physiology

Background:

• Panic disorder patients experience panic attacks after sodium lactate infusions.
• The mechanism behind lactate-induced panic attacks is not fully understood.
• Lactate can induce panic-like responses in rats with impaired GABA neurotransmission in the dorsomedial hypothalamus (DMH).

Purpose of the Study:

• To investigate the role of circumventricular organs (CVOs), specifically the organum vasculosum lamina terminalis (OVLT) and subfornical organ (SFO), in detecting plasma lactate levels.
• To determine if CVOs activate the DMH to mediate lactate-induced panic-like responses.
• To identify the neuroanatomical basis for the lactate response in panic disorder.

Main Methods:

• Rats with chronic dysfunction of GABA neurotransmission in the DMH received lactate infusions.
• Cannulae were implanted into the DMH, OVLT, SFO, or median preoptic area (MePOA).
• Artificial cerebrospinal fluid (ACSF) or tetrodotoxin (TTX) was injected into CVO sites, followed by lactate infusions. Direct lactate injections into the OVLT were also performed.

Main Results:

• Tetrodotoxin (TTX) injection into the OVLT completely blocked the lactate-induced panic-like response.
• TTX injections into the SFO or MePOA did not block the response.
• Direct lactate injections into the OVLT elicited anxiety-like responses in rats.

Conclusions:

• The OVLT is likely the primary site for detecting lactate infusions.
• The OVLT activates a compromised DMH, leading to anxiety-like responses.
• This study provides the first neuroanatomical evidence linking the OVLT to lactate-induced panic responses.