Long-Term Effects of Juvenile NMDAr or DAr Antagonism on Adolescent Reward-Related Neurobehavioral Outcomes

Previous research from our laboratory found a critical period of development between postnatal day (P)18-P24 in which synaptogenesis occurs with the emergence of spatial performance. Subjects were treated with the dopamine receptor antagonist, flupenthixol or the NMDAr antagonist, MK-801 from P18-P24 and were tested in an operant conditioning procedure during adolescence. Another group of subjects were given the same drugs prior to each acquisition session to test immediate effects. Spine densities for the early treatment groups were quantified to measure structural changes in the NAc and c-Fos labeling were quantified after an DA or NMDA agonist to measure receptor desensitization. Early flupenthixol increased locomotor activity during acquisition, which corresponded with an increase in DAr sensitization in the NAc. No behavioural or structural differences were found between the early MK-801 group and saline control. Late flupenthixol decreased operant acquisition and locomotor activity, while late MK-801 increased both.