Investigations into the nature of a 7-OH-DPAT discriminative cue: comparison with D-amphetamine

In the present study, separate squads of rats were trained to discriminate either the dopamine D3 receptor preferring ligand 7-hydroxy-2-(di-N-propylamino)-tetralin (7-OH-DPAT) (0.03 mg/kg) from saline, or D-amphetamine (0.3 mg/kg) from saline using a standard operant schedule (FR10 schedule reinforcement). Following stable acquisition of responding, tests of generalisation and antagonism were conducted. A number of dopamine agonists having high dopamine D2-like receptor (D2, D3 or D4) affinity generalised to the 7-OH-DPAT, but not amphetamine, cue. The dopamine D2/3 receptor agonist SKF38393 showed no generalisation to either drug cue. Subsequent correlational analysis suggested that this effect was most likely mediated through the dopamine D3 receptor. The dopamine D2/3 receptor antagonist raclopride significantly attenuated both cues. The failure of these drugs to generalise to amphetamine, suggest that there is little involvement of the dopamine D3 receptor subtype in mediating its discriminative stimulus properties.