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Latent inhibition in rats neonatally treated chronically with MK-801: differential effects on conditioned taste
Ryo Niikura1, Takashi Nozawa1, Kazuo Yamada1
1Institute of Psychology and Behavioral Neuroscience, University of Tsukuba, Tennoudai 1-1-1, Tsukuba 305-8577, Ibaraki, Japan.
Abstract:
Chronic neonatal blockade of N-methyl-d-aspartate (NMDA) receptors produces various abnormal behaviors in adulthood animals. This study investigated the effects of neonatal treatment chronically with MK-801 in rats on the preexposure-induced retardation of CS-US association, i.e. latent inhibition (LI), of two aversive classical conditioning tasks in adulthood. In conditioned taste aversion (CTA) using sucrose taste and LiCl, neonatal chronic MK-801 (0.4 mg/kg twice/day) treatment attenuated the inhibitory effect of sucrose preexposure on the aversive conditioning, although the treatment did not affect CTA conditioning itself. On the other hand, in conditioned emotional response (CER) using tone and electrical foot shock, rats neonatally treated with MK-801 showed the same degree of inhibitory effect of tone preexposure on the aversive conditioning compared with neonatally vehicle-treated rats, and also showed the same level of CER conditioning itself. Thus, the effect of chronic neonatal blockade of NMDA receptors on the LI of classical conditioning in adulthood was differentiated by the task employed. Results suggest that LI of CTA paradigm compared with that of CER is more sensitive to abnormal development after chronic neonatal blockade of NMDA receptors as an index of cognitive/attentional deficits caused by the treatment.
Insights
Neonatal blockade of N-methyl-d-aspartate (NMDA) receptors impairs latent inhibition in taste aversion learning but not in fear conditioning in adult rats. This suggests task-dependent cognitive deficits following early NMDA receptor disruption.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Developmental Neuroscience
Background:
- Chronic neonatal blockade of N-methyl-d-aspartate (NMDA) receptors is known to induce behavioral abnormalities in adulthood.
- Latent inhibition (LI) is a form of associative learning where prior exposure to a stimulus retards later conditioning.
Purpose of the Study:
- To investigate the impact of neonatal chronic MK-801 treatment on latent inhibition (LI) in two distinct aversive classical conditioning tasks in adult rats.
- To determine if the effects of neonatal NMDA receptor blockade on LI are task-dependent.
Main Methods:
- Rats received chronic neonatal treatment with MK-801 (an NMDA receptor antagonist) or vehicle.
- Adult rats were tested on conditioned taste aversion (CTA) and conditioned emotional response (CER) paradigms.
- Latent inhibition was assessed by comparing conditioning in pre-exposed versus non-pre-exposed groups.
Main Results:
- Neonatal MK-801 treatment significantly attenuated the latent inhibition effect in the conditioned taste aversion (CTA) task.
- However, the same treatment did not affect latent inhibition in the conditioned emotional response (CER) task.
- Neither CTA nor CER conditioning itself was affected by the neonatal treatment.
Conclusions:
- Chronic neonatal blockade of NMDA receptors differentially affects latent inhibition depending on the classical conditioning task.
- The conditioned taste aversion paradigm appears more sensitive to developmental cognitive/attentional deficits induced by early NMDA receptor blockade compared to the conditioned emotional response paradigm.
