OPIOID MODULATION OF ATTENTION-RELATED RESPONSES - PERIPHERAL-TO-CENTRAL PROGRESSION AND DEVELOPMENT OF MU-INFLUENCE AS LEARNING OCCURS

Endogenous opioids modulate attention-related bradycardiac responses e voked by novel stimuli and Pavlovian conditioned signals, and these ef fects are distinct from those of endogenous opioids on memory. We inve stigated the role of peripheral opioid receptors in modulating attenti on and Pavlovian learning, in rabbits tested for bradycardiac orientin g responses to novel tones, and for Pavlovian conditioning and extinct ion of cardiac discrimination. Pretraining, IV treatment with the opia te antagonist naloxone-HCl (0.1-0.5 mg/kg) facilitated initial develop ment of Pavlovian conditioned discrimination and delayed its later ext inction, compared to saline vehicle, as previously observed. Pretraini ng treatment with its peripherally acting analog, quaternary naloxone- methiodide (1.29-6.47 mg/kg), also promoted initial development, but n ot extinction, of discrimination, and it reduced the magnitude of brad ycardiac orienting responses and of tachycardiac unconditioned respons es. Treatment with the selective mu-antagonist peptide CTOP (10-30 mu g/kg) facilitated conditioned responses and reduced unconditioned resp onses, somewhat later during training, but it did not reliably affect extinction or orienting responses. These results confirm an important role of peripheral opioids in regulating attentional and associative f unctions involved in orienting and the earliest stage of Pavlovian lea rning, prior to development of central opioid regulation of later asso ciative, hedonic and mnemonic functions. These findings also suggest t hat cardiovascular opioid receptors might mediate peripheral opioid in fluences on attention and early association formation, via modulation of cardiac responses to stimuli and autonomic sensory feedback to the brain.