Studies on electroencephalogram (EEG) in rats suggest that moderate doses of cocaine or d-amphetamine activate D1 rather than D2 receptors.
The effects of cocaine and d-amphetamine, two psychomotor stimulant drugs with pronounced addictive properties, on the electroencephalogram (EEG) of rats were studied by telemetric recordings from the skull in non-anesthetized, freely moving rats. The electrocorticogram (ECoG) was recorded. Both cocaine (10 mg/kg IP) and d-amphetamine (0.4 mg/kg IP) produced a desynchronization, characterized by a general lowering in power in all of the frequency bands. These effects of both drugs were mimicked by the selective agonist at D1 receptors SK&F 38393 (3 mg/kg SC) and were reversed by the antagonist at D1 receptors SCH 23390 (0.2 mg/kg IP) but not influenced by haloperidol (0.1 mg/kg IP) in a dose which is likely to block D2 rather than D1 receptors. These doses of cocaine or d-amphetamine did not produce stereotyped behaviour and slight, if any, increases in locomotor activity only. Large doses of cocaine (30 mg/kg IP) or d-amphetamine (4 mg/kg IP) produced stereotyped behaviour and alterations in EEG which are, based on previous own studies, characteristic for additional stimulation of D2 receptors. This was manifest in a selective increase in power of the alpha-1 band. A similar effect was also produced by the agonist both at D1 and D2 receptors, apomorphine (0.5 mg/kg SC). These results suggest that moderate, but probably rewarding doses of cocaine or d-amphetamine mainly activate D1 dopamine receptors. This activation might be relevant for the rewarding properties of these drugs.
Ferger
B
B
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany.
Kropf
W
W
Kuschinsky
K
K
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013239:Stereotyped Behavior / Q000187:drug effects
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003042:Cocaine; D003913:Dextroamphetamine