UC San Diego

Activation of the maternal innate immune response during pregnancy increases risk of schizophrenia, an illness with elevated rates of drug addiction. Measures of drug effects upon brain reward function are provided by intracranial self-stimulation (ICSS) reward thresholds. In order to better understand effects of MIA on an offspring’s sensitivity to drugs of abuse, we examined effects of MIA on amphetamine facilitation of ICSS reward threshold under both acute and withdrawal states.

The objective of this thesis project was to determine MIA effects upon amphetamine facilitated ICSS reward threshold during both the acute and withdrawal phases following investigator-administered amphetamine injection. Pregnant Sprague-Dawley rats were injected with polyinosinic:polycytidylic acid (poly I:C 8mg/kg), lipopolysaccharide (LPS 50μg/kg), or saline (control). Adult offsprings’ ICSS reward thresholds were measured acutely, 10 minutes after investigator-administered amphetamine (0.125, 0.25, and 0.5 mg/kg subcutaneous), and during the withdrawal phase 8 and 12 hours following daily amphetamine injections (4mg/kg x 4 days).

MIA was found to significantly attenuate the direct acute effects of amphetamine upon brain reward threshold. Thus, MIA offspring require more drug to achieve similar drug reward effect. Additionally, MIA attenuates the magnitude of ICSS withdrawal response across repeated bouts of intoxication/withdrawal. Higher drug consumption to achieve intoxication, and less aversion to continued drug consumption generated by a blunted withdrawal effect may work in tandem to enhance addiction risk in MIA offspring. Identification of the mechanisms underlying this effect may contribute to prevention, treatment, and understanding of prognosis in human addictions.