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.