| abstract |
Methods and compositions for modulating GABA release in a subject are provided. A preferred embodiment provides a composition containing an effective amount of an ErbB4 ligand to enhance or promote GABA release, i.e., GABAergic transmission. The ErbB4 ligand can be an agonist ligand or an antagonist ligand depending on the disorder to be treated. Representative disorders that can be treated include, but are not limited to epilepsy, depression and anxiety, insomnia, stroke, pain, bipolar, autism, or a combination thereof. Exemplary agonist ligands include Er1, variants thereof,antibodies to ErbB4, and antibody fragments that bind to ErbB4. Exemplary antagonist ligands include the extracellular domain of ErbB4 and fusion proteins thereof. The extracellular domain of ErbB4 binds to endogenous Er1 and thereby reduces or inhibits GABA release. Methods for treating neurological disorders are also provided. Preferred methods include administering an effective amount of an ErbB4 agonist ligand to a subject in need thereof to promote or enhance GABA release in the subject. By increasing GABA release a sedative effective can be induced in the subject. Methods for inducing a stimulatory effect in a subject are also provided. In these methods, an effective amount of an ErbB4 antagonist ligand is administered to subject to reduce or inhibit GABA release in the subject. |