Effects of low, autoreceptor selective doses of dopamine agonists on the discriminative cue and locomotor hyperactivity produced by d-amphetamine.
The ability of low doses of the dopamine (DA) agonists quinpirole and (+)-3-PPP to reduce the discriminative stimulus properties and locomotor hyperactivity produced by d-amphetamine (0.5 mg/kg) was assessed in two groups of rats. Quinpirole (0.0125-0.05 mg/kg) and (+)-3-PPP (1.0-2.0 mg/kg) completely antagonized d-amphetamine-induced locomotor hyperactivity. In contrast, only single doses of quinpirole (0.025 mg/kg) and (+)-3-PPP (2.0 mg/kg) were effective in the drug discrimination paradigm; the antagonisms were small (18-47%), but significant. The inhibitory effects of quinpirole and (+)-3-PPP in these behavioural models are probably due to their ability to selectively stimulate DA autoreceptors in the nucleus accumbens and reduce the increase in DA release produced by d-amphetamine. It is suggested that the much weaker effects of the drugs in the discrimination paradigm are due to changes produced by the long-term periodic administration of d-amphetamine to these animals, such as a down-regulation in the sensitivity of DA autoreceptors.
Department of Psychology, University of Reading, United Kingdom.
L
L
Furmidge
Z Y
ZY
Tong
N
N
Petry
D
D
Clark
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D003913:Dextroamphetamine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D015259:Dopamine Agents; D004873:Ergolines; D010880:Piperidines; D011954:Receptors, Dopamine; D019257:Quinpirole; C026539:preclamol; D003913:Dextroamphetamine