Alterations in striatal dopamine overflow during rotational behavior induced by amphetamine, phencyclidine, and MK-801.
A Mele, D Fontana, A Pert
Synapse July 1997 DOI: 10.1002/(sici)1098-2396(199707)26:3<218::aid-syn3>3.0.co;2-a (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats with unilateral 6-OHDA lesions of the medial forebrain bundle |
| Interventions | Amphetamine Phencyclidine (PCP) MK-801 |
| Key findings | Amphetamine, PCP, and MK-801 each produced comparable ipsilateral rotational behavior, but striatal dopamine overflow in the intact striatum rose about 130% with amphetamine, about 30% with PCP, and not at all with MK-801. The authors argue that rotation can occur without striatal dopamine elevation and suggest PCP's effects in this model may be mediated mainly by NMDA blockade. |
Abstract
Rats lesioned unilaterally in the medial forebrain bundle with 6-OHDA rotated ipsilateral to the lesion following injections of amphetamine, phencyclidine (PCP), and MK-801. Concurrent measurement of striatal dopamine (DA) in the intact striatum with in vivo microdialysis revealed a dissociation between rotational behavior and alterations in DA overflow induced by the three drugs. Amphetamine produced robust ipsilateral rotational behavior and a substantial elevation in striatal DA (approximately 130% increase at asymptote). PCP produced comparable increases in rotational behavior, but only approximately 30% increase in striatal DA. MK-801 also had a comparable behavioral effect but failed to alter DA overflow in the intact striatum. Since MK-801, a noncompetitive NMDA antagonist which does not enhance extracellular dopamine in the striatum, is able to produce ipsilateral rotational behavior in rats with unilateral nigrostriatal lesions, it is likely that the effects of PCP may also be determined predominantly through NMDA blockade in this model.