Desensitization of 5-hydroxytryptamine-facilitated dopamine release in vivo

Desensitization to serotonin (5-hydroxytryptamine, 5-HT)-facilitated dopamine release in vivo develops following either continuous or repeated pulses of 5-HT. For instance, an initial 20 min pulse of 5-HT (10 microM) produced a 715 +/- 150% increase in basal dopamine, an effect which steadily declined over 5 subsequent fractions to 222 +/- 80%. Also, secondary pulses (s2) of 5-HT administered 40 min following the primary pulse (s1), elicited a 327 +/- 16% increase in dopamine levels, significantly decreased from the primary s1 pulse. Augmentation of either protein kinase A or protein kinase C systems attenuated 5-HT-facilitated dopamine release, suggesting a role for protein kinases in regulating the desensitization process.