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Endogenous opioids modulate attention-related bradycardiac responses evoked by novel stimuli and Pavlovian conditioned signals, and these effects are distinct from those of endogenous opioids on memory. We investigated the role of peripheral opioid receptors in modulating attention and Pavlovian learning, in rabbits tested for bradycardiac orienting responses to novel tones, and for Pavlovian conditioning and extinction of cardiac discrimination. Pretraining, IV treatment with the opiate antagonist naloxone-HCl (0.1-0.5 mg/kg) facilitated initial development of Pavlovian conditioned discrimination and delayed its later extinction, compared to saline vehicle, as previously observed. Pretraining treatment with its peripherally acting analog, quaternary naloxone-methiodide (1.29-6.47 mg/kg), also promoted initial development, but not extinction, of discrimination, and it reduced the magnitude of bradycardiac orienting responses and of tachycardiac unconditioned responses. Treatment with the selective mu-antagonist peptide CTOP (10-30 microg/kg) facilitated conditioned responses and reduced unconditioned responses, 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 functions involved in orienting and the earliest stage of Pavlovian learning, prior to development of central opioid regulation of later associative, hedonic and mnemonic functions. These findings also suggest that cardiovascular opioid receptors might mediate peripheral opioid influences on attention and early association formation, via modulation of cardiac responses to stimuli and autonomic sensory feedback to the brain.

Endogenous opioids modulate attention-related heart rate responses evoked by novel stimuli and conditioned signals in ways that differ from their better-known effects on motivation and memory functions. We investigated the role of delta-opioids in modulating bradycardiac orienting and Pavlovian conditioned responses in rabbits, following i.v. treatment with the highly selective delta-receptor antagonist naltrindole (NTI; 0.037-0.370 mg/kg). When administered immediately before testing, NTI induced modest but detectable effects: the lowest dose increased cardiac discrimination near the end of the first training session, whereas the higher doses of NTI impaired discrimination, compared to saline-treated controls. NTI treatment immediately before testing also appeared to promote habituation of bradycardiac orienting responses elicited by novel tones, but NTI did not alter unconditioned heart rate responses following tone-shock pairs or extinction of conditioned responses. In contrast, the low dose of NTI administered 20 min, rather than immediately before testing, facilitated conditioned bradycardia during extinction, as well as during training. These results provide evidence that endogenous delta-opioid modulators normally delay the disappearance of bradycardiac orienting responses during habituation, inhibit or promote the development of bradycardiac conditioned responses during Pavlovian training depending on dose, and promote the disappearance of conditioned responses during extinction. These findings suggest that endogenous delta-opioid activity, probably involving both peripheral and central systems, coincides with, and may reflect, uncertainty about stimulus significance.

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A lesson using digital sums that allows teachers to assess students' understanding of reasoning, arithmetic, and geometry.