The effects of dopaminergic agonists and antagonists on the frequency-response function for hypothalamic self-stimulation in the rat.
The function of dopaminergic synapses in generating the reinforcing effect of brain stimulation was examined in 8 rats. The animals were implanted with bipolar electrodes and trained to press a bar for lateral hypothalamic stimulation. The frequency of stimulation pulses was systematically changed, and a frequency-response curve was plotted for each rat after intraperitoneal injection of a test agent. Dopamine agonists and antagonists selective to either D1 or D2 subtypes of receptors were used. The curve was shifted to a high-frequency range by either SCH 23390 (D1 antagonist) or raclopride (D2 antagonist). SKF 38393 (D1 agonist) failed to shift the curve, and quinpirole and CV 205-502 (D2 agonists) shifted the lower part of the curve to a low-frequency range. The results suggest that an activation of D2 receptors generates a reinforcing effect, and that the effect is expressed only if D1 receptors are activated to an optimal level.
Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.
S
S
Nakajima
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NB
O'Regan
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004567:Electrodes, Implanted; D004873:Ergolines / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D020891:Raclopride; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012201:Reward; D012457:Salicylamides / Q000494:pharmacology; D012653:Self Stimulation / Q000187:drug effects*
D000634:Aminoquinolines; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D020891:Raclopride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C046650:quinagolide