From the Research
Inhibiting glutamatergic neurons in the amygdala can be achieved through various pharmacological approaches, with the most recent and highest quality study suggesting that targeting GPR17 in the basolateral amygdala to ventral hippocampal CA1 glutamatergic projection may be a novel potential target for therapy of anxiety disorders 1.
Mechanisms of Inhibition
Several mechanisms can inhibit glutamatergic neurons in the amygdala, including:
- Enhancing GABA activity using benzodiazepines like diazepam (5-10mg daily) or alprazolam (0.25-0.5mg three times daily) 2
- Directly blocking glutamate receptors using NMDA receptor antagonists such as ketamine (at subanesthetic doses of 0.5mg/kg IV) 3
- Reducing glutamate release using lamotrigine (starting at 25mg daily, gradually increasing to 200mg daily over several weeks) 2
- Targeted optogenetic or chemogenetic techniques for more precise inhibition 4
Clinical Applications
Inhibiting glutamatergic neurons in the amygdala can be valuable for treating conditions involving amygdala hyperactivity, including:
- Anxiety disorders
- PTSD
- Certain forms of epilepsy
- Neuropathic pain and anxiety behaviors induced by paclitaxel chemotherapy 4
Recent Findings
A recent study found that GPR17 modulates anxiety-like behaviors via basolateral amygdala to ventral hippocampal CA1 glutamatergic projection, and that inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors 1. Another study found that CaMKII neurons in the amygdala are critical for neuropathic pain and anxiety behaviors induced by paclitaxel chemotherapy, and that selectively inhibiting these neurons alleviated anxiety behavior without affecting motor activity 4.