Opiate states of memory: receptor mechanisms.
The present studies characterized the receptor mechanisms of morphine-induced states of memory. Morphine (5 mg/kg) produced a state in which rats could learn and retrieve an operant response; retrieval was impaired, however, when the rats were tested in the normal state. Conversely, rats that were trained in the normal state failed to retrieve the response in the morphine state. In either case the mnesic state was dose dependent, commencing at morphine doses as low as 0.8 mg/kg. In rats trained with 5 mg/kg of morphine, retrieval was fully adequate when tested with this same dose but not when tested with either lower or higher doses. Naloxone, but not naltrindole, antagonized the morphine-induced state; heroin and (-)-cyclazocine, but not U50,488H, (+)-cyclazocine and SNC80, produced a state in which retrieval occurred at least partially. Time-effect studies in which injections were made from 0 to 240 min before the sessions indicated that the retrieval in saline-to-morphine and morphine-to-saline conditions occurred along different time courses; a theory of opiate signal transduction suggests that these temporal profiles result from morphine producing two bi-directional mnesic states that may differ as much as the analgesia and hyperalgesia that morphine also induces. It appears that a particular magnitude of mu opiate receptor activation produces a state to which a memory trace can be confined in a highly selective manner. The normal and this particular morphine state are only some of the many mutually inaccessible and molecularly definable states of memory that are likely to exist, thus challenging the unitary concept of an individual organism's memory.
Bruins Slot
L A
LA
Centre de Recherche Pierre Fabre, F 81106 Castres Cedex, France.
Colpaert
F C
FC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D011957:Receptors, Opioid / Q000502:physiology*
D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D009020:Morphine