Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. I. Behavioral and biochemical studies.
Bilateral 6-hydroxydopamine (6-OHDA) lesions in the nucleus accumbens of rats induced motor hypoactivity 7 days after the lesion. Spontaneous functional recovery of this impaired behavior occurred in 3-4 weeks. Behavioral and biochemical studies suggest that the hypoactivity is due to damage of the dopamine systems in the nucleus accumbens. The 6-OHDA lesions induced a decrease in the nucleus accumbens levels of dopamine and its metabolites of about 30% both 7 and 20 days after the lesion. The in vitro uptake of [3H]dopamine in nucleus accumbens tissue of the 6-OHDA-lesioned rats was decreased to the same extent at 7, 14 and 28 days after the lesion. Scatchard analysis of [3H]haloperidol binding studies in nucleus accumbens tissue revealed a shift from one type of binding site in tissue of sham-lesioned rats to two types of binding sites in tissue of 6-OHDA-lesioned rats 29 days after the lesion. This shift was not present in nucleus accumbens tissue 8 days after a 6-OHDA lesion. The spontaneously recovered rats showed an enhanced behavioral response upon administration of the dopamine agonist apomorphine. The present data suggest that the spontaneous functional recovery of impaired motor activity is caused by the development of supersensitivity of the dopamine receptor systems in the nucleus accumbens. This supersensitivity may be the result of increased affinity of one type of binding site or an increased number of functional binding sites.
Wolterink
G
G
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Van Zanten
E
E
Kamsteeg
H
H
Radhakishun
F S
FS
Van Ree
J M
JM
D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006220:Haloperidol / Q000378:metabolism; D006892:Hydroxydopamines; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009714:Nucleus Accumbens / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology*; D012686:Septal Nuclei / Q000502:physiology*
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D016627:Oxidopamine; D006220:Haloperidol; D004298:Dopamine