In vitro studies have widely demonstrated that the abundance and availability of G-protein-coupled receptors (GPCRs) at the cell surface is regulated by the neuronal environment and is the result of complex intraneuronal trafficking. However, this regulation is still poorly understood in vivo. Modulation of receptor availability at the neuronal membrane is a key event in the regulation of neuronal functions (e.g. neurotransmitter release or neuronal excitability in physiological, pathological or therapeutic conditions). We discuss the effects of duration of receptor stimulation (acute versus chronic) on the intraneuronal trafficking of GPCRs in vivo, and we show that this trafficking might differ according to subcellular compartment (soma, dendrites or axon terminals).