Targeting beta-2 adrenergic receptor attenuates schizophrenia-like behavioral effects induced by ketamine in mice: cAMP/PKA/BDNF-PEA-3 and RIM-1α signaling pathways involvement
Saudi Pharmaceutical Journal April 1, 2026 Mohammed M. Heikal, Ahmed F. Mohamed, Nora O. Abdel Rasheed et al.
Formoterol, a drug typically used for asthma, showed neuroprotective effects in a mouse model of schizophrenia-like behaviors induced by ketamine. It reduced anxiety, improved social interaction, and reversed anhedonia, while also restoring neurotransmitter balance and enhancing learning and memory. The drug reduced neuroinflammation and oxidative stress, and modulated synaptic plasticity by boosting the cAMP/PKA/BDNF signaling pathway, which increased expression of genes and proteins involved in synaptic function, including glutamate receptor subunits and regulators like PSD-95 and synaptophysin. These effects were blocked by a PKA inhibitor, confirming the pathway's role. Formoterol may be a promising candidate for treating synaptic dysfunction in schizophrenia.