Article

Opioid Regulation of Pavlovian Overshadowing in Fear Conditioning

Department of Psychology and Brain Research Institute, University of California, Los Angeles, USA.
Behavioral Neuroscience (Impact Factor: 3.25). 08/2010; 124(4):510-9. DOI: 10.1037/a0020083
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ABSTRACT In Pavlovian overshadowing, a stimulus that predicts a biologically important event reduces conditioning to another, equally predictive stimulus. We tested the effects of an opioid antagonist and dopamine agonist on the ability of a salient white noise to overshadow a less salient light. Rats were conditioned to fear a light or a noise-light compound using a mild footshock. Compound-conditioned rats trained under the saline vehicle revealed significant overshadowing of the light by the noise. This overshadowing effect was significantly attenuated in rats trained under the opioid antagonist naltrexone, consistent with an opioid-mediated negative feedback model of conditioning. In line with predictions made by negative feedback-type models, we failed to obtain overshadowing with few trials, suggesting that the processes underlying conditioning during initial trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained in our preparation. Lastly, we compared the involvement of dopamine-mediated and opioid-mediated processes in overshadowing by conditioning rats under the partial dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both naltrexone and SKF 38393 were found to attenuate overshadowing; however, the behavioral profiles produced by each pharmacological manipulation were distinct. Collectively, these studies demonstrate an important role for both opioid- and dopamine-mediated processes in multiple-trial overshadowing.

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    • "It has been suggested that D 1 antagonism may be important for the behavioral effects of antipsychotics and may be secondary to D 2 antagonism (Josselyn et al, 1997; Miller, 1990, 2009). A potential role for D 1 in AMP disruption of LI is consistent with studies in rats implicating D 1 in overshadowing, a related measure of salience allocation, other behavioral effects of AMP in other species, as well as a more general role for midbrain D 1 in attentional accuracy (Liu et al, 2010, 2011; O'Tuathaigh and Moran, 2002; Zelikowsky and Fanselow, 2010). Translation of the outcome of experiments using animal model systems to human psychosis and its treatment must include the caveat of species and environmental differences from the human condition. "
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