Role of NMDA, opioid and dopamine D1 and D2 receptor signaling in the acquisition of a quinine-conditioned flavor avoidance in rats

- Flavored fructose, saccharin and quinine (0.03%) elicited short-term avoidance.
- Dopamine D1 antagonism during acquisition prolonged quinine-conditioned avoidance.
- Opioid antagonism during acquisition prolonged quinine-conditioned avoidance.
- NMDA antagonism during acquisition prolonged quinine-conditioned avoidance.
- Dopamine D2 antagonism during acquisition failed to affect quinine avoidance.

A conditioned flavor preference (CFP) can be produced by pairing a flavor (conditioned stimulus, CS +) with the sweet taste of fructose. Systemic dopamine (DA) D1, D2 and NMDA, but not opioid, receptor antagonists significantly reduce the acquisition of the fructose-CFP. A conditioned flavor avoidance (CFA) can be produced by pairing a CS + flavor with the bitter taste of quinine. To evaluate whether fructose-CFP and quinine-CFA share common neurochemical substrates, the present study determined the systemic effects of DA D1 (SCH23390: SCH), DA D2 (raclopride: RAC), NMDA (MK-801) or opioid (naltrexone: NTX) receptor antagonists on the acquisition of quinine-CFA. In Experiment 1, food-restricted male rats were trained over 8 alternating one-bottle sessions to drink an 8% fructose + 0.2% saccharin solution (FS) mixed with one flavor (CS −, e.g., grape) and a different flavor (CS +, e.g., cherry) mixed in a solution (FSQ) containing fructose + saccharin and quinine at 0.001-0.030% concentrations. In six subsequent two-bottle choice tests (1-3: two sessions each) with the CS − and CS + flavors presented in FS solutions, only rats trained with 0.03% quinine displayed a CS + avoidance in Test 1. In Experiment 2, rats received vehicle (Veh), SCH (200 nmol/kg), RAC (200 nmol/kg), MK-801 (100 μg/kg) or NTX (1 mg/kg) 30 min prior to the 8 one-bottle training sessions with CS −/FS and CS +/FSQ (0.03% quinine) solutions. An additional vehicle group (Veh 0.06%) was trained with a CS +/FSQ containing 0.06% quinine. In the two-bottle choice tests, the Veh and RAC groups avoided the CS + flavor in Test 1 only, whereas the SCH, MK801, and NTX groups significantly avoided the CS + in Tests 1-3. The Veh.06% group trained avoided the CS + in Tests 1 and 2, but not Test 3. In Experiment 3, Veh and SCH groups were trained as in Experiment 2, but were tested with CS flavors presented in 0.2% saccharin solutions. The SCH group avoided the CS + flavor in Tests 1-3 while the Veh group avoided the CS + in Test 1 only. Thus whereas DA D1, DA D2 and NMDA, but not opioid receptor antagonism blocked acquisition of sweet taste-based CFP, DA D1, NMDA and opioid, but not DA D2 receptor antagonism enhanced the CFA produced by the bitter taste of quinine.