Dopamine receptor antagonists block amphetamine and phencyclidine-induced motor stimulation in rats.
d-Amphetamine (DEX) and phencyclidine (PCP) increased motor activity in rats as measured in automated activity cages. Analysis of the stimulation indicated that both drugs increased horizontal activity (total activity), locomotion, and peripheral activity. However, DEX increased while PCP decreased the incidence of rearing. The ability of different drugs to antagonise DEX- and PCP-induced increases in total activity (called stimulation) was measured. Dopamine (DA) D1 receptor antagonists (SCH23390, NNC-01-0112) were 7-8 times more potent in blocking DEX than PCP. DA D2 receptor antagonists (raclopride, remoxipride, haloperidol) were only 1-2 times more potent against DEX-induced stimulation. Nonselective DA receptor antagonists were also tested. Chlorpromazine was more potent against DEX than against PCP. Buspirone and sertindole were slightly more potent in blocking PCP than DEX. Ritanserin (5-HT2 receptor antagonist) was inactive against both stimulants. 8-OH-DPAT (5-HT1A receptor agonist) potentiated the stimulant effects of DEX and PCP. Prazosin (alpha 1-adrenergic receptor antagonist) partially blocked both DEX and PCP. Most drugs tested depressed spontaneous motor activity. Remoxipride and sertindole, however, caused very little depression even at doses several times higher than those needed to block DEX or PCP. The data show clear pharmacological differences between DEX- and PCP-induced stimulation.
Jackson
D M
DM
Department of Behavioural Pharmacology, CNS Preclinical Research and Development, Södertälje, Sweden.
Johansson
C
C
Lindgren
L M
LM
Bengtsson
A
A
D000818:Animals; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists; D013268:Stimulation, Chemical
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012702:Serotonin Antagonists; D010622:Phencyclidine; D003913:Dextroamphetamine