Rewarding effects of AMPA administration into the supramammillary or posterior hypothalamic nuclei but not the ventral tegmental area.
We examined whether injections of the excitatory amino acid AMPA are rewarding when injected into the posterior hypothalamus and ventral tegmental area. Rats quickly learned to lever-press for infusions of AMPA into the supramammillary or posterior hypothalamic nuclei but failed to learn to lever-press for similar injections into the ventral tegmental areas. AMPA injections into the supramammillary nucleus, but not the ventral tegmental area, induced conditioned place preference. The rewarding effects of AMPA appear to be mediated by AMPA receptors, because coadministration of the AMPA antagonist CNQX blocked the rewarding effects of AMPA, and administration of the enantiomer R-AMPA did not mimic the rewarding effects. AMPA injections into the supramammillary nucleus, but not the ventral tegmental area, also increased extracellular dopamine concentrations in the nucleus accumbens. Pretreatment with the D1 dopamine antagonist SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] led to extinction of AMPA self-administration. These findings implicate posterior hypothalamic regions in reward function and suggest that reward mechanisms localized around the ventral tegmental area are more complex than has been assumed recently.
Ikemoto
Satoshi
S
Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. sikemoto@intra.nida.nih.gov
Witkin
Brian M
BM
Zangen
Abraham
A
Wise
Roy A
RA
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D007034:Hypothalamus, Posterior / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007267:Injections; D008297:Male; D008326:Mammillary Bodies / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D004298:Dopamine