Inhibition of passive-avoidance memory formation in the day-old chick by the opioid cytochrophin-4.
Cytochrophin-4 (cyt-4), a tetrapeptide with opioid-like activity, caused amnesia when injected into chick forebrain 5 hr after passive-avoidance training. Bilateral injections of cyt-4 directly into the lobus parolfactorius (LPO) resulted in the chicks being amnesic for the training task 24 hr later, whereas unilateral injections of cyt-4 were effective only when injected into the right LPO. Cyt-4-induced amnesia was reversed by the general opioid antagonist, naloxone, indicating that cyt-4 was acting via an opioid receptor. The mu- and delta-opioid receptors (but not kappa-opioid or ORL(1)-receptors) have been shown to be involved in memory formation 5 hr after training (). Because an antagonist of the mu-opioid receptor inhibited memory, we attempted to reverse the effect of cyt-4 using mu-opioid receptor agonists. Met[enk] was unable to reverse the inhibition of memory formation by cyt-4 suggesting that the mu-opioid receptor is not involved in this effect. However endomorphin-2 (endo-2) reversed the effect of cyt-4. We further investigated the action of endo-2 using an irreversible antagonist of the mu-receptor, beta-funaltrexamine (beta-FAN), and found that endo-2 reversed beta-FAN-induced amnesia indicating that endo-2 was not acting on the mu-opioid receptor in the chick. Because unilateral injections of beta-FAN were not amnesic (bilateral injections were amnesic) this provided further evidence that the effect of cyt-4 was not mediated via the mu-opioid receptor. Coinjection of the delta-receptor agonist, (D-Pen(2), L-Pen(5))enkephalin (DPLPE), reversed the disruptive effect of cyt-4 on memory. However, memory modulation via the delta-opioid receptor was not lateralized to the right hemisphere suggesting that cyt-4 does not act via this receptor either. It was shown that an antagonist of the epsilon-opioid receptor inhibited memory at the 5 hr time point. We conclude that the epsilon-opioid receptor or an unidentified opioid receptor subtype could be involved in the action of cyt-4.
Division of Biochemistry, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia.
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Freeman
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Young
D000367:Age Factors; D000647:Amnesia / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology*; D002645:Chickens; D004723:Endorphins / Q000494:pharmacology*; D005260:Female; D008024:Ligands; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors
D004723:Endorphins; D008024:Ligands; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C043460:epsilon receptor; D009270:Naloxone; C061451:cytochrophin-4