LAUSR

Studies of humans, mammalian animals, and chicks reveal that embryonic opioid exposure (EOE) changes the response to pharmacological rewards in postnatal individuals, which may be an outcome of permanent alterations to neural systems. However, the mechanism behind this alteration remains unclear. GABA transmitter has a trophic effect on early GABAergic neuronal development, and EOE decreases GABA concentration in developing brains. Here, we determined whether the development of inhibitory transmission was affected by EOE and whether altered GABA release was the underlying mechanism. We revealed that morphine administration in the early but not the late embryonic period decreased inhibitory transmission in the striatum of chicks. Meanwhile, day-old chicks with early embryonic morphine exposure showed increased psychomotor activity after acute morphine injection compared with saline-exposed chicks. Furthermore, GABA injection in the chick embryo following morphine administration mitigated damage to GABA transmission and recovered the behavioral response to acute morphine injection in chicks. Collectively, our findings suggest that abnormal GABA release in the early embryonic period induced by opioid exposure is attributable to functional and structural developments of the GABA synapse, and that the dysfunction of striatal GABA transmission may be linked to enhanced psychomotor response during initial drug exposure in postnatal life.