Prenatal morphine exposure increases gamma oscillation and theta coherence in the rat reward system.

Previous studies have found that prenatal morphine (PNM) exposure leads to both increased and decreased risk of substance abuse in offspring. Understanding more about the neurobiological changes after the PNM exposure would help to understand more about this issue. Signaling from dopamine neurons of the ventral tegmental area (VTA) in the mesoaccumbal and mesocortical pathways plays a vital role in drug dependency. To provide further knowledge about the effects of PNM on drug seeking behavior and the dopamine system. We recorded local field potentials (LFP) simultaneously in the VTA, NAc (nucleus accumbens), BLA (basolateral amygdala) and mPFC (medial prefrontal cortex) in male adult rats prenatally treated with saline or morphine. Morphine (10 mg/kg) induced conditioned place preference (CPP) establishment, extinction and priming were tested to investigate the effects of PNM on addictive-like behavior. In addition, the expression of nuclear histone deacetylases (HDAC4, HDAC5), which plays essential epigenetic roles in neuroplasticity after drug use were also tested in VTA and NAc. The results showed that PNM did not change the acquisition of morphine CPP in male rats, but impaired CPP extinction and morphine (5 mg/kg) - primed reinstatement of CPP after extinction. PNM increased the low gamma (30-60 Hz) and high (60-90 Hz) gamma LFP powers in NAc and BLA. PNM also leads to increased theta (4-9 Hz) coherence between VTA and NAc, and increased HDAC5 expression in VTA. After chronic morphine administration, coherence between VTA-NAc, mPFC-NAc and mPFC-BLA increased significantly in PNS rats, but no changes were find in PNM rats, indicating impaired plasticity in brain circuits. All these results suggest that PNM exposure increased reward processing in adult male rats, but impaired morphine CPP extinction and reinstatement, which relate to decreases network plasticity and increased HDAC5 expression in the reward system.