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Characterizing withdrawal in rats following repeated drug administration using an amphetamine-vehicle-haloperidol
J R Stadler1, W F Caul, R J Barrett
1Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA. stadlejr@ctrvax.vanderbilt.edu
Rationale:
Previous research using an amphetamine (AM)-haloperidol (HA) drug- drug discrimination task has shown that predominant responding on the HA-appropriate lever occurs 24 h after a single or multiple administrations of 10 mg/kg AM. Conversely, rebound responding on the AM-appropriate lever occurs following single or multiple administrations of 1 mg/kg HA. HA-appropriate responding was also observed 24 h following a single injection of AM using a three-lever, AM-vehicle-HA discrimination task. However, a single administration of HA did not produce robust rebound responding on the AM-appropriate lever. The present studies seek to clarify the discrepancy between responding following HA in the two- and three-choice tasks.
Objective:
Experiment 1 examined the extent of rebound responding that could be achieved following ten daily administrations of either 10 mg/kg AM or 1 mg/kg HA. Experiment 2 explored potential differences between the two- and three-choice tasks in characterizing the post-HA cue.
Methods:
Animals were trained to discriminate 0.35 mg/kg AM, vehicle, and 0.033 mg/kg HA. In experiment 1, animals received ten daily injections of 10 mg/kg AM, vehicle, or 1 mg/kg HA, and were tested 24 h after the final injection, and again 8, 15, and 22 days post-treatment. In experiment 2, animals were retrained and then treated daily with either vehicle or 1.0 mg/kg HA for 10 days, and then tested 24 h after the final injection, and again 5 and 11 days post-treatment, with either all three levers or with only the AM- and HA-appropriate levers available.
Results:
In experiment 1, multiple injections of AM produced robust HA lever responding, which is consistent with results from previous studies that used the two-choice, AM-HA discrimination task. However, multiple injections of HA did not produce predominant responding on the AM-appropriate lever. In experiment 2, animals treated with either vehicle or HA responded predominantly on the vehicle-appropriate lever when tested with all three levers present. When tested with the vehicle lever removed, however, animals treated with vehicle responded predominantly on the HA-appropriate lever, whereas those treated with HA responded predominantly on the AM-appropriate lever.
Conclusions:
These results suggest that the two-choice and three-choice task used here differ in how the post-HA withdrawal cue is characterized. This finding emphasizes the importance of knowing the relative locations of the agonist-, vehicle-, and antagonist-produced cues on the interoceptive stimulus continuum established by discrimination training.