Abstract | RATIONALE: OBJECTIVES: To test further the hypothesis that D4 receptor blockade can reduce motor hyperactivity, behavioral effects of three chemically and pharmacologically dissimilar D4 antagonists were compared to that of ketanserin, a serotonin 5-HT(2A/2C) antagonist. METHODS: Selective dopamine lesions were made in male rats at postnatal day (PD) 5 with intracisternal 6-hydroxydopamine (100 microg) after desipramine pretreatment (25 mg/kg, SC) to protect noradrenergic neurons. Effects of D4 receptor-selective antagonists and ketanserin on lesion-induced motor hyperactivity were examined during the periadolescent period (postnatal days 23-26) with an infrared photobeam activity system. RESULTS: The D4 antagonists L-745,870 and U-101,958 dose-dependently inhibited motor hyperactivity in rats with neonatal lesions, whereas S-18126 lacked this effect at doses up to 30 mg/kg. None of these drugs affected motor behavior in sham control rats. In contrast, ketanserin produced apparent sedative effects in both lesioned and intact control rats without normalizing hyperactivity. CONCLUSIONS:
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Authors | Kehong Zhang, Eugen Davids, Frank I Tarazi, Ross J Baldessarini |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 161
Issue 1
Pg. 100-6
(Apr 2002)
ISSN: 0033-3158 [Print] Germany |
PMID | 11967637
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- Drd4 protein, rat
- Receptor, Serotonin, 5-HT2A
- Receptors, Serotonin
- Receptors, Dopamine D4
- Oxidopamine
- Ketanserin
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Topics |
- Animals
- Animals, Newborn
- Attention Deficit Disorder with Hyperactivity
(drug therapy)
- Dopamine Antagonists
(pharmacology, therapeutic use)
- Dopamine D2 Receptor Antagonists
- Dose-Response Relationship, Drug
- Ketanserin
(pharmacology)
- Male
- Motor Activity
(drug effects)
- Oxidopamine
- Rats
- Receptor, Serotonin, 5-HT2A
- Receptors, Dopamine D4
- Receptors, Serotonin
(drug effects, physiology)
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