"Priming" to dopamine agonist-induced contralateral turning as a model of non-associative sensitization to the expression of the post-synaptic dopamine message.
In adult rats bearing unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic neurons, a single administration of a dopamine (DA) receptor agonist results in strong sensitization ("priming") of contralateral turning in response to D2 and particularly D1 receptor agonists. In order to investigate the role of distinct environmental cues associated with the effect of the agonist during exposure to the primer, rats bearing 15-day-old unilateral 6-OHDA lesions were primed in their home cage with L-dopa or with saline. L-Dopa but not saline induced medium to low but steady contralateral turning. Three days later, challenge with the D1 agonist SKF 38393 in the home cage also resulted in contralateral turning in the rats previously primed with L-dopa, but not in those primed with saline. In a second experiment rats lesioned with 6-OHDA were primed in two different contexts (hemispheres versus cylinders) with a single administration of the D2/D3 agonist quinpirole (LY 171555: 0.2mg/kg s.c.) or saline. Three days later the rats were placed in hemispheres and tested for contraversive turning in response to saline or to SKF 38393. SKF 38393 elicited high rate contraversive turning independently of the environment where priming with quinpirole took place; on the other hand no conditioned contraversive turning was observed after saline. In a third experiment, the possibility of priming SKF 38393-induced turning by stimulation of nigral or striatal DA receptors was investigated. Rats lesioned unilaterally with 6-OHDA were locally infused on the lesioned side in the substantia nigra with SKF 38393 or in the striatum with quinpirole. Both these treatments elicited contralateral turning, the intranigral injection of SKF 38393 eliciting a stronger and longer lasting contraversive turning than intrastriatal quinpirole. Challenge with SKF 38393 (3mg/kg s.c.) 3 days later induced contralateral turning only in rats previously primed with intrastriatal quinpirole. The results of these studies are consistent with the idea that "priming" is an example of non-associative sensitization induced by stimulation of denervated striatal DA receptors and expressed as an increased efficiency of post-synaptic dopaminergic transduction in the striatum.
Department of Toxicology, University of Cagliari, Viale A. Diaz 182, 09100 Cagliari, Italy.
M.
M
Morelli
S.
S
Fenu
A.
A
Pinna
A.
A
Cozzolino
A.
A
Carta
G.
G
Di Chiara