Well, I don't know about motivation in general but I do know a little about neurotransmitters and drug addiction:
We have a nice balance between neurotransmitters released in the pre-synaptic neurons with the corresponding receptors in the post-synaptic neuron. The relative "abundance" of neurotransmitters and receptor molecules can change, for example by the presence of drugs which mimic neurotransmitters. Chronic exposure to these drugs in the synapse can cause either the availability of neurotransmitter to decline or receptor molecules to decline since the drug "hyper-activates" the synapse. The neurons "adapts" to this by reducing the number of receptors or neurotransmitter molecules available to the synapse.
Now imagine removing the drug. The synapse now has a deficiency of chemical transmitters.
Because of this, the "efficiency" of nerve signal relay within the synapse is degraded causing "fatigue" of one sort or another. This "motivates" the drug abuser to seek more drugs in an effort to re-establish prior synaptic flow and is a significant factor in the "withdrawal" symptoms they experience when getting off of drugs.
Perhaps other forms of "motivation" can likewise be described in terms of synaptic neurophysiology.