The role of NT1 receptor agonism in discriminative stimulus properties of a D1 or D2 dopamine receptor agonist

Neurotensin is a 13 amino acid fragment of a much larger 170 amino acid precursor protein. In the CNS, it is found co-localized with dopamine receptors in much of the mesocorticolimbic pathway. These findings correlate with the pathophysiology of schizophrenia in which afflicted patients display significantly lower neurotensin in their cerebral spinal fluid and that these levels increase after treatment by antipsychotic drugs(APD). To date, analogs of neurotensin are the only existing agonists that can cross the blood-brain barrier and act in the CNS by binding to NTR1 receptors. These analogs have allowed for animal testing in numerous APD screening paradigms such as conditioned avoidance response and pre-pulse inhibition. The results suggest that these analogs mirror atypical APD effects and avoid deficits in cognition. This study aimed to identify the neurotensin agonist PD149163's relationship to the discriminate cues of groups of rats trained to discriminate either the D1 agonist SKF81297 or the D2 agonist quinpirole from saline respectively. The results showed that PD149163 suppressed response rates in both groups and failed to engender generalized responding. PD149163 also failed to disrupt generalized responding to the training drugs, suggesting that neurotensin does not mediate the interoceptive stimulus effects that are elicited by dopamine D1 or D2 receptor agonism.