The novel dopamine D4 receptor agonist (PD 168,077 maleate): doses with different effects on locomotor activity are without effect in classical conditioning

Conditioning is normally selective to the most likely predictors of motivationally significant events and some dopamine (DA) agonists produce dysfunction in this process. Moreover, the DA D(4) receptor is implicated in normal and abnormal functions that have some dopaminergic basis (e.g., in attention deficit hyperactivity disorder and schizophrenia). We therefore used locomotor activity to identify doses of a novel D(4) receptor agonist (PD 168,077) with contrasting behavioral effects (over the range 0.064-1 mg/kg). Doses that either did (0.064 mg/kg) or did not (0.5 mg/kg) significantly increase activity were then tested using aversive and appetitive procedures, in which conditioning was reflected in decreased and increased response rates, respectively. Associating a signal with food or foot shock is normally reduced in trace conditioning, when stimulus events are separated in time. Similarly, animals normally learn relatively little about background stimuli that do not well predict food delivery or the onset of shock. Both doses of PD 168,077 were without effect on conditioning, whether appetitive or aversive, and irrespective of how informative the predictive stimulus was. Thus, we find no evidence that the D(4) receptor has any likely effect on associative learning or its disorder. Furthermore, D(4)-mediated hyperactivity was dissociable from cognitive effects.