Brain neuromediator systems in the immune response control: pharmacological analysis of pre- and postsynaptic mechanisms.
The involvement of the dopaminergic (DAergic), GABAergic and serotoninergic (5-HTergic) synaptic mechanisms in neuroimmunomodulation are considered. It is shown that the central DA- and GABAergic systems exert a stimulatory influence on the immune reactivity. Activation of postsynaptic DA receptors with apomorphine and (+)(3-hydroxyphenyl)-N-n-propylpiperidine [(+)-3-PPP] at high doses, D2 receptor activation with quinpirole, as well as DA reuptake blockade with amantadine and bupropion, resulted in an increase in the immune response. The intensity of the immune response was also increased during activation of the GABAergic system with the GABA agonist muscimol or the benzodiazepine agonists diazepam and tazepam. On the other hand, decreases in the activity of either system by different drugs inhibiting DAergic and GABAergic neurotransmission (antagonists of DA postsynaptic receptors haloperidol at 1.0 mg/kg and (-)-3-PPP at 6.8 mg/kg, agonists of DA autoreceptors apomorphine at 0.02 mg/kg, (-)- and (+)-3-PPP at 1.7 and 3.4 mg/kg, antagonist of GABA receptors bicuculline, blocker of chloride channels picrotoxin, blockers of benzodiazepine receptors Ro 15-1788 and Ro 15-3505) produce suppression of the immune response. The 5-HTergic system is involved in the inhibitory mechanism of neuroimmunomodulation. 5-HT reuptake blockade with 4-(5,6-dimethyl-R-benzophuranil)-piperidine (CGP-6085A) and sertraline led to immunosuppression.
Devoino
L
L
Institute of Physiology, Novosibirsk, Timakova, Russian Federation.
Idova
G
G
Alperina
E
E
Cheido
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology*; D004298:Dopamine / Q000502:physiology; D006462:Hemolytic Plaque Technique; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015213:Neuroimmunomodulation / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D017661:Receptors, Presynaptic / Q000187:drug effects*; D012397:Rosette Formation; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012756:Sheep / Q000276:immunology; D013569:Synapses / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D004298:Dopamine; D007075:Immunoglobulin M; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D017661:Receptors, Presynaptic; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D005680:gamma-Aminobutyric Acid