Involvement of dopamine D2 receptors in apomorphine-induced facilitation of forebrain serotonin output.
The effect of systemic administration of the nonselective dopamine receptor agonist apomorphine on efflux of serotonin (5-hydroxytryptamine, 5-HT) in striatum and hippocampus of freely moving rats was examined using in vivo microdialysis. 5-HT efflux was increased by a moderate dose of apomorphine sufficient for a postsynaptic dopaminergic effect (0.5 mg/kg, s.c.), but not by a lower dose (0.1 mg/kg, s.c.), that acts preferentially on presynaptic dopamine receptors. This effect was blocked by a dopamine D2 receptor antagonist raclopride, administered either systemically or locally into striatum, but not by a 5-HT1A receptor antagonist N-¿2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl¿-N-(2-pyridinyl) cyclohexanecarboxamide 3HCI (WAY-100635). This indicates that dopamine D2 receptors, and not 5-HT1A receptors, mediate the facilitatory effect of apomorphine, and that this effect occurs at the nerve terminal level. Behavioral effects of apomorphine outlasted the concomitant changes in 5-HT efflux, suggesting that these changes resulted from dopaminergic receptor activation, rather than from the drug-induced behavioral arousal.
Program in Neuroscience, Princeton University, NJ 08544-1010, USA. annam@princeton.edu
A
A
Mendlin
F J
FJ
Martín
B L
BL
Jacobs
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D001058:Apomorphine