Behavioral and biochemical effects of intra-accumbens dopaminergic grafts.
6-Hydroxydopamine (6-OHDA) lesions in the ventral tegmental area (VTA) in rats prevented the hyperactivity response to methamphetamine in an open field. Transplantation of mesencephalic dopaminergic cells, obtained from rat embryos, into the nucleus accumbens (NAC) of 6-OHDA-lesioned animals restored the hyperactivity 4 weeks after grafting. By microdialysis of the NAC in freely moving rats no significant differences in baseline concentration of dopamine (DA) among the 3 groups (control, lesioned, grafted) were observed. However, after methamphetamine administration, DA increased significantly during the first 80 min in control animals, during the first 40 min in grafted animals, but did not increase in lesioned animals. On the other hand baseline concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased to one sixth to one third of those of controls in 6-OHDA-lesioned animals, and they did not respond to methamphetamine. After grafting, however, DOPAC and HVA restored to control levels and responded to methamphetamine with decreases as was observed in control animals. Data suggest that grafts not only restore the ability to release DA but also improve DA metabolism in the NAC. This might be a reason for recovery of locomotor activity.
Ishida
Y
Y
Department of Psychiatry, Miyazaki Medical College, Japan.
Hashitani
T
T
Kumazaki
M
M
Ikeda
T
T
Nishino
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006085:Graft Survival; D006892:Hydroxydopamines; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000502:physiology / Q000637:transplantation*; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009498:Neurotoxins; D009714:Nucleus Accumbens / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000502:physiology*
D006892:Hydroxydopamines; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D016627:Oxidopamine; D004298:Dopamine