Haloperidol and clozapine antagonise amphetamine-induced disruption of latent inhibition of conditioned taste aversion.
BACKGROUND
Latent inhibition (LI) describes a process by which repeated pre-exposure of a stimulus without any consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that LI is impaired in rats and in humans by injections of the indirect dopamine agonist amphetamine (AMPH), and that this disruption can be prevented by co-administration of either the typical neuroleptic haloperidol (HAL) or the atypical neuroleptic clozapine (CLZ).


OBJECTIVE
Most of what is known of the pharmacology of LI is derived from studies using either the conditioned emotional response or the conditioned active avoidance paradigm. The goal of the present study was to determine whether these results would generalize to the conditioned taste aversion assay.


METHODS
We tested whether AMPH (0.5 mg/kg) pretreatment would disrupt LI of a conditioned aversion to sucrose, and if so, which stage of the procedure is critical for mediating the disruption; in addition, we tested whether HAL (0.2 mg/kg) or CLZ (5.0 mg/kg) could restore such an expected LI disruption.


RESULTS
We determined that AMPH disrupted LI when it was injected before pre-exposure and prior to conditioning, but not if the rats were injected before either stage alone. When HAL or CLZ was given 40 min before AMPH (before both pre-exposure and conditioning), it blocked LI disruption.


CONCLUSIONS
These results are in line with the pharmacology of LI as derived from other conditioning paradigms. We conclude that the pharmacological regulation of LI in the CTA paradigm is similar to what has been observed previously in the conditioned emotional response and the conditioned active avoidance paradigms.
Russig
Holger
H
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Schorenstrasse 16, 8603, Schwerzenbach, Switzerland.
Kovacevic
Aneta
A
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Schorenstrasse 16, 8603, Schwerzenbach, Switzerland.
Murphy
Carol A
CA
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Schorenstrasse 16, 8603, Schwerzenbach, Switzerland.
Feldon
Joram
J
Laboratory of Behavioral Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Schorenstrasse 16, 8603, Schwerzenbach, Switzerland. feldon@behav.biol.ethz.ch.
D018663:Adrenergic Agents; D000661:Amphetamine / Q000037:antagonists & inhibitors*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013649:Taste / Q000187:drug effects*
D018663:Adrenergic Agents; D014150:Antipsychotic Agents; D000661:Amphetamine; D003024:Clozapine; D006220:Haloperidol