The Synaptic Button and Drug Action

The synapse of the terminal button, both pre- and post-synaptically (that is, from transmitting to receiving button) are also effected by a mechanism called hyperpolarization of the dendritic autoreceptors where they are activated by neurotransmitter or antagonist drug action (that binds to and blocks the receptors) thereby reducing the rate of firing of the neuron, effectively acting as an antagonist (Carlson, 2010, p. 113). Certainly, drugs that block the autoreceptors antagonistically, reduce the effect of hyperpolarization (which is regulatory by nature) and thereby work as agonists (reducing this regulatory effect) (p. 113).

Drugs can affect synaptic transmission in a variety of ways. Carlson (2010) mentions at least 11 ways, ranging from drugs serving as precursor agonists (like L-Dopa on dopamine), inhibits synthesis of neurotransmitter antagonist (like PCPA on serotonin), prevents storage of neurotransmitter in vesicles as antagonist (reserpine on monoamines), stimulates release of neurotransmitter as agonist (spider venom on acetylcholine-ACh), inhibits release of neurotransmitter as antagonist (toxin on ACh), stimulates postsynaptic receptors as agonists (nicotine and muscarine on ACh), and naturally several others like blocks as antagonists, blocks or stimulates autoreceptors, blocks reuptake as agonists, or inactivates as agonists that which is transmitted synaptically. Certainly, the two basic forms of these are agonists and antagonists (drugs that are facilitating versus inhibiting postsynaptic effects) (p. 111).

Drug reactivity in tolerance and sensitization are both similar and different (compensatory mechanisms v. direction of effect). Drug reactions are similar in these two phenomena because drugs follow a dose-response curve that reciprocates larger drug effects with increase doses, up to a maximum effect, where dose increases no longer produce drug reactivity, and increase prevalence of side effects and risk (p. 107). Drug effects that diminish with repeated dosage are called tolerance; and effects that increase are called sensitization (p. 108). Drug tolerance effects are the bane of illicit drug users (think heroine), in that the brain works to maintain optimal levels of functioning at all times and with repeated (and increasing) doses of exogenous substances, the brain produces opposite reactions to compensate (hence the opposite withdrawal symptoms upon substance stop) (p. 109). Further, the sites where the substances bind become less sensitive to the drug as it is used more frequently and the receptors actually decrease in number, also knows as a compensatory mechanism (similar to the decrease in effectiveness of coupling, another compensatory mechanism) (p. 109). In contrast to tolerance mechanisms, sensitization is more rare (p. 109). Because sensitization causes ever-larger drug effects, compensatory mechanisms direct regulatory efforts away from physiologic processes, as in respiratory depressive effects of barbiturates or opiates that show sensitization (especially in combination) versus their euphoric and/or analgesic properties that show tolerance effects (p. 109).


References
Carlson, N. (2010). Physiology of behavior, (10th ed.). Boston: Allyn & Bacon.