title: Repeated pretreatment of morphine prevents morphine-induced amnesia: A possible involvement for dorsal hippocampal NMDA receptors.
abstract: BACKGROUND
  Learning and memory processes can be affected by morphine administration. It has been previously demonstrated that the effects of morphine depend on the timing of drug administration. In the present study, the effects of microinjections of a NMDA receptor agonist and antagonist into the CA1 regions of the dorsal hippocampi (intra-CA1) on repeated pretreatment of morphine-induced prevention of morphine-induced amnesia have been investigated.
  
  
  METHODS
  Step-through inhibitory avoidance task of memory has been used to examine retrieval of memory formation, 24 h after training in male Wistar rats.
  
  
  RESULTS
  The results indicate that post-training administration of morphine (7.5 mg/kg) impaired memory retrieval, but not in the animals, which received previous repeated morphine (7.5 and 10 mg/kg) injections followed by morphine withdrawal. Repeated co-administration of NMDA (7.5 and 10 ng/rat, intra-CA1) with an ineffective dose of morphine (5 mg/kg), once daily for three days reversed morphine-induced amnesia. Repeated bilateral intra-CA1 microinjections of NMDA, once daily for three days followed by a five-day washout had no effect on the expression of amnesia produced by post-training morphine. Three-day administration of the NMDA receptor antagonist, D-AP5 (0.5 - 2 µg/rat, intra-CA1) followed by a five-day washout had no effect on morphine-induced amnesia. On the other hand, intra-CA1 microinjections of the same doses of D-AP5 prior to injection of 7.5 mg/kg of morphine (per day×3 days) decreased the reversal of morphine-induced amnesia.
  
  
  CONCLUSIONS
  These data imply that the dorsal hippocampal NMDA receptor mechanism(s) may modulate the effect-induced by repeated morphine administration on a challenge dose of morphine-induced amnesia.
authors.affiliation: Department of Pharmacology, Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Iran. Iran.zarinmr@ams.ac.ir
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zarrindast
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Asadi
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology*; D000647:Amnesia / Q000139:chemically induced* / Q000517:prevention & control*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D004334:Drug Administration Schedule; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007266:Inhibition, Psychological; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine