Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynapticGABA(B) responses in mice lacking GABA(B(1))

GABA(B) (gamma -aminobutyric acid type B) receptors are important for keepi ng neuronal excitability under control. Cloned GABA(B) receptors do not sho w the expected pharmacological diversity of native receptors and it is unkn own whether they contribute to pre- as well as postsynaptic functions. Here , we demonstrate that Balb/c mice lacking the GABA(B(1)) subunit are viable , exhibit spontaneous seizures, hyperalgesia, hyperlocomotor activity, and memory impairment. Upon GABA(B) agonist application, null mutant mice show neither the typical muscle relaxation, hypothermia, or delta EEG waves. The se behavioral findings are paralleled by a loss of all biochemical and elec trophysiological GABA(B) responses in null mutant mice. This demonstrates t hat GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) r eceptors and casts doubt on the existence of proposed receptor subtypes.