Memory enhancement in mice: role of drug dose and training-testing interval.
Pharmacologic probes are useful for studying memory mechanisms. For eight drug treatments affecting a variety of transmitter systems [arecoline, piribedil, clonidine, fluoxetine, naloxone, ACTH (4-10)], we determined how long memory retention would remain improved with a dose sufficient to improve 3-hour retention. While all 6 treatments enhanced 3-hour retention test performance at p less than 0.05, only 5 treatments significantly enhanced retention 24 hour after training and none of the treatments significantly affected retention at 168 hours. A detailed analysis of the dose and retention interval interaction for arecoline indicated that at low doses retention decreased as the retention interval increased while higher doses improved retention up to 3 hours and only the highest dose tested enhanced retention at 3 and 24 hours. Drug doses that enhance short-term retention (3 hours) were not adequate to enhance long term retention (168 hours). The 6 drug treatments had no significant or systematic effect on activity or on acquisition. We conclude that short-term retention performance was better because of enhanced memory processing or recall and not because of performance effects per se.
Flood
J F
JF
Geriatric Research, Education and Clinical Center, VA Medical Center, Sepulveda, CA 91343.
Smith
G E
GE
Cherkin
A
A
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001115:Arecoline / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010891:Piribedil / Q000494:pharmacology; D013997:Time Factors
D010446:Peptide Fragments; D005473:Fluoxetine; D009270:Naloxone; D001115:Arecoline; D000324:Adrenocorticotropic Hormone; D010891:Piribedil; C011394:ACTH (4-10); D003000:Clonidine