Differences between d-methamphetamine and d-amphetamine in rats: working memory, tolerance, and extinction.
BACKGROUND
Previously, we have shown that d-amphetamine (AMPH) was more potent than d-methamphetamine (METH) at increasing extracellular levels of dopamine (DA) in the prefrontal cortex (PFC) at doses that had similar effects in the nucleus accumbens. Since working memory depends on PFC DA, it was postulated that AMPH would also be more potent than METH at affecting working memory.


OBJECTIVE
To determine if AMPH is more potent than METH at affecting working memory.


METHODS
Working memory was measured in adult female Sprague-Dawley rats using a delayed-alternation T-maze task with multiple delays (1, 10, 60 s) and food rewards. The percentage of food rewards consumed was also recorded. Animals were tested with METH and AMPH before and after a chronic protocol, with measurements of locomotor activity used to test for pharmacological tolerance or sensitization. The effects of METH and AMPH on extinction were also examined by omitting the food rewards from the T-maze. RESULTS. Both METH and AMPH produced dose-related bimodal effects on working memory at the intermediate delay (10 s); however, AMPH was more potent than METH. Both METH and AMPH initially also decreased the percentage of food rewards consumed in the T-maze. After chronic testing, animals displayed tolerance to both the working memory impairments and the reduction in food reward intake produced by AMPH. Animals did not display significant tolerance to the effects of METH on food reward consumption and performed worse in the T-maze after chronic testing. METH, but not AMPH, interfered with extinction.


CONCLUSIONS
These results indicate that METH and AMPH differ in altering working memory and the expression of tolerance, perhaps due to differences in behavioral inhibition.
Shoblock
James R
JR
Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Avenue (MC-136), Albany, NY 12208, USA. ShobloJ@mail.amc.edu
Maisonneuve
Isabelle M
IM
Glick
Stanley D
SD
D000662:Amphetamines / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005108:Extinction, Psychological / Q000187:drug effects*; D005260:Female; D006185:Habituation, Psychophysiologic; D018782:Maze Learning; D008570:Memory, Short-Term / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D000662:Amphetamines; D000697:Central Nervous System Stimulants; D008694:Methamphetamine