Infralimbic D2 Receptor Influences on Anxiety-like Behavior and Active Memory/attention in CD-1 Mice

Ventromedial prefrontal cortical (vmPFC) dopamine (DA) influences attentional aspects of cognition and anxiety-like behavioral responding in rodents. The present study investigated the role of D2 receptors on spontaneous alternation in the Y-maze and anxiety-like behavior in a two-trial elevated plus-maze (EPM) procedure in CD-1 mice following vmPFC infusions of the D2 antagonist, sulpiride, and the D2 agonist, quinpirole. Pretrial 1 quinpirole infusions did not influence any anxiety measure (with the exception that the lowest dose increased protected stretch attends), but reduced protected exploration activity (closed-arm entry/time ratios and wall rearing). In Trial 2 24 h later (no injection), quinpirole exerted an anxiolytic behavioral profile relative to Trial 2 control mice (enhanced open-arm entry/time ratios, unprotected head dips), with no effects on protected exploration or risk assessment activity. Pretrial 1 sulpiride infusions enhanced unprotected exploration (open-arm entry/time ratios, unprotected stretch attend, and head dips), but did not influence protected exploration or risk assessment in the EPM. In Trial 2, 24 h later (no injection), sulpiride extended this anxiolytic profile to reduced protected exploration and risk assessment activity (closed-time ratio, protected stretch attend, and head dips). In the Y-maze, whereas quinpirole disrupted alternation performance (5- and 10-nmol dose) concomitant with marked repetitive same-arm returns (SAR) at the highest dose, sulpiride disrupted alternation performance concomitant with marked repetitive SAR behavior at the lowest dose only. These data indicate that although infralimbic (IL) quinpirole and sulpiride infusions similarly disrupted alternation performance in the Y-maze and reduced Trial 2 anxiety-like responding in the EPM, these drugs differentially produced these effects.