ABSTRACT
The process of synaptic transmission is the key target for all psychoactive drugs. Transmission may be influenced by drugs affecting the synthesis, storage, release, inactivation, and postsynaptic effects of transmitter substances. Further, drugs effective in major psychiatric illnesses such as depression and schizophrenia have prominent effects on transmission mediated by biogenic amines such as dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5HT; serotonin). The past decade has seen marked advances in our understanding of key features of the transmission process mediated by these amines. Of particular importance is the emerging concept that transmission mediated by these substances appears, at least in part, to occur through diffusion-mediated signaling, termed extrasynaptic or volume transmission (VT). Also, it is now recognized that the inactivation process of reuptake,
mediated by specific transporters located in the plasma membrane, plays the key role in regulating the concentration of these amines in the extracellular fluid (ECF). Furthermore, these protein transporters are not merely constitutive membrane components but undergo a variety of regulatory processes. Finally, in the past decade it has become more accepted, even if still not completely understood, that effects of released amines can be influenced by other peptide transmitters colocalized in the same neurons. Our emerging concepts of the functioning of transporters and the processes of cotransmission and VT have not been well integrated into current views of psychoactive drug action. Yet it is likely that they influence profoundly the effects produced by such drugs. Because of this, it is appropriate to view such processes from the perspective of their potential neuropsychopharmacologic impact.
