Prenatal ethanol exposure attenuates GABAergic inhibition in basolateral amygdala leading to neuronal hyperexcitability and anxiety-like behavior of adult rat offspring.
Prenatal exposure to a relatively high-dose ethanol (EtOH) caused anxiety-like behavior of adult male rat offspring. Previous studies have demonstrated that GABA system in the basolateral amygdala complex (BLA) is involved in the pathogensis of anxiety-related disorders. The role of GABAergic system in the BLA was investigated in anxiety-like behavior evoked by prenatal EtOH exposure. The infusion of midazolam (MDZ), a positive modulator of GABA(A) receptor, into the BLA prevented anxiety-like behavior in EtOH-offspring without affecting the corresponding behavior of control offspring. The data suggest that anxiety-like behavior could be causally related to increased neuronal excitability attributable to depressed GABAergic inhibition in the BLA. To test this hypothesis, evoked potential was studied using brain slices from EtOH-offspring. Potential evoked in the BLA by single stimuli applied to external capsule showed multispike responses, indicative of GABAergic disinhibition. These multiple responses were no longer evident after the perfusion with MDZ. In the slices from EtOH-offspring, paired-pulse inhibition (GABA(A)-dependent) was suppressed. Also, in EtOH-offspring, long-term potentiation (LTP) was induced by a single train of high frequency stimulation, which did not induce LTP in control rats. Moreover, MDZ pretreatment prevented the facilitating effect of EtOH on LTP induction. The data provide the functional evidence that prenatal EtOH exposure attenuates GABAergic inhibition in the BLA resulting in neuronal hyperexcitability and anxiety-like behavior of adult rat offspring.
Zhou
R
R
Department of Physiology, Nanjing Medical University, Hanzhong Road 140, Jiangsu, PR China. zhou-rong@hotmail.com
Wang
S
S
Zhu
X
X
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D055233:Cornified Envelope Proline-Rich Proteins; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007441:Intubation, Gastrointestinal; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D055233:Cornified Envelope Proline-Rich Proteins; C524534:Sprr1b protein, mouse; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D008874:Midazolam