Latent inhibition of the classically conditioned rabbit nictitating membrane response is unaffected by the NMDA antagonist MK801

Abstract

Induction oflong-term potentiation, a putative substrate for behavioral plasticity, appears to be dependent on NMDA receptor activation. Blockade ofNMDA receptor activity has been shown to impair both classical conditioning and spatial cognition. The present study evaluated the effects of NMDA-receptor blockade by MK801 on latent inhibition of the classically conditioned nictitating membrane response in rabbits. Nonreinforced preexposure to a tone conditioned stimulus retarded acquisition rates in subjects pretreated with either saline or MK8010 Thus, latent inhibition does not appear to be mediated by or dependent on NMDA activity or related NMDAdependent long-term potentiation. Findings are discussed in relation to potential substrates for latent inhibition.Long-tenn potentiation (LTP) of synaptic transmission is a prominent candidate for a neurobiological mechanism underlying behavioral plasticity. LTP occurs in brain systems known to playa significant role in learning, such as the hippocampus (Bliss & Gardner-Medwin, 1973), and LTP-like changes develop as a consequence of stimulus pairings during associative learning (Berger, Alger, & Thompson, 1976;G. B. Robinson, 1992;Weisz, Clark, & Thompson, 1984). Moreover, prior potentiation of hippocampal synapses has been shown to facilitate acquisition of conditioned responses (CRs) (Berger, 1984;G. B. Robinson, Port, & Berger, 1989). The induction of L TP at both hippocampal CAl and dentate granule cell synapses appears to be dependent on N-methyl-n-aspartate (NMDA) receptors (Collingridge, Kehl, & McLennan, 1983;Harris, Ganong, & Cotman, 1984). Antagonists of NMDA-mediated activity have been reported to impair both LTP (G. B. Robinson & Reed, 1992) and classical conditioning (G. B. Robinson, 1993) in the rabbit, as well as perfonnance on the Morris milk maze (Heale & Harley, 1990), spontaneous alternation (Walker & Gold, 1991), and operant conditioning with differential reinforcement oflow rates of responding (Tonkiss, Morris, & Rawlins, 1988) in rats.The research reported here was supported by grants from the Natural Sciences and Engineering Research Council of Canada (G.B.R.). We would like to thank Marni Turnbull for her expert assistance with portions of these experiments. Requests for reprints should be addressed to G.

Novel factors contributing to the expression of latent inhibition.

“…In our 5-psi data set, by contrast, early learning was identical for the LI and sit groups, but rabbits preexposed to the CS eventually reached asymptote at lower CR levels. The Experiment 1 findings are very similar to those reported previously using similar stimulus parameters (Robinson, Port, & Stillwell, 1993), and they may provide an explanation of why many previous eyeblink conditioning experiments successfully reported LI effects: The successful earlier LI studies and the present study used either a shock US or a relative intense airpuff US. Also, many studies used percentage of CRs or total numbers of CRs (i.e., measures of overall CR performance across trials) as the measure of LI (e.g., Salafia & Allan, 1980, 1982Solomon, Brennan, & Moore, 1974;Solomon, Lohr, & Moore, 1974;Solomon & Moore, 1975) instead of (or in addition to) reporting trials to a conditioning criterion (i.e., a measure of rate of initial learning).…”

Prediction, perception, and psychosis: Application of associative learning theories to schizophrenia research.

“…That is, there is also evidence for intact LI (e.g., Aguado et al, 1994 Experiment 3b; J. A. Davis & Gould, 2005; Robinson et al, 1993; Schroeder et al, 1998; Tenn et al, 2005; Traverso et al, 2003, 2012 Experiment 1; Turgeon et al, 1998; Weiner & Feldon, 1992) and even enhanced LI (Gaisler-Salomon et al, 2008; Gaisler-Salomon & Weiner, 2003; Pålsson et al, 2005) after the administration of these drugs. Thus, different NMDA receptor antagonists, with different doses and schedules of administration, appear to have variable effects on LI, possibly affecting different psychological mechanisms supporting LI (for reviews, see Moser et al, 2000; Weiner & Arad, 2009).…”

Latent inhibition in animals as a model of acute schizophrenia: A reanalysis.

“…In this context, note that LI has been found not t o be disrupted by the potent psychostimulant phencyclidine (Weiner & Feldon, 1992; see also Robinson, Port, & Stillwell, 1993, for a similar result, but using the glutamatergic antagonist MK-801). To our knowledge, there are no available data concerning LI and ketamine, another potent psychostimulant closely related t o phencyclidine.…”