ISSN:
1432-2072
Keywords:
Rotational behavior
;
8-OH-DPAT
;
RU 24969
;
Serotonin
;
Dopamine
;
Raphe
;
6-Hydroxydopamine
;
Denervation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the ascending nigro-striatal pathway have been shown to rotate in response to dopamine (DA) agonists that are not considered to have postsynaptic DA stimulant properties in intact animals, suggesting a relative loss of DA receptor selectivity in the denervated striatum. The present experiments assessed the possibility that this loss of selectivity may extend to serotonin (5HT) agonist drugs. The 5HT-1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at doses of 0.3–3 mg/kg SC, induced robust contralateral rotational behavior (RB) in 6-OHDA-lesioned rats that had been preselected on the basis of high responsiveness to the atypical DA agonists 3-PPP and SKF 38393. Rats with unilateral dorsal raphe lesions induced by 5,7-dihydroxytryptamine (5,7-DHT) showed contralateral RB in response to similar doses of 8-OH-DPAT but with a different behavioral pattern. The putative 5HT-1b agonist RU 24969 produced contralateral RB in 5,7-DHT-lesioned rats while showing a much weaker effect in 6-OHDA-lesioned rats. Striatal DA levels were depleted by 99% in representative 6-OHDA-lesioned rats but striatal 5HT levels were unaffected. The effects of 8-OH-DPAT in 6-OHDA-lesioned rats were therefore not attributable to destruction of ascending 5HT-containing neurons. These effects may result from indirect actions, mediated by 5-HT neurons or neuronal receptors, that result from asymmetry of brain DA systems. Alternatively, it is proposed that rats with highly denervated striatal DA receptors show a loss of apparent molecular selectivity such that weak partial DA agonist properties of 8-OH-DPAT, although not demonstrable in normal rats, become manifested under these conditions.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00176841
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