A new proposal for drug conditioning with implications for drug addiction: the Pavlovian two-step from delay to trace...

Pavlovian conditioning of drug effects is generally acknowledged to be a critical factor in the development and persistence of drug addiction. In drug conditioning the focus has essentially been on one type of Pavlovian conditioning, namely, delay conditioning in which the CS and drug UCS overlap and are temporally contiguous. Another type of Pavlovian conditioning is trace-conditioning in which the CS terminates before the onset of the UCS. While trace conditioning has been extensively studied in conditioning studies using a punctual CS and a non-drug UCS, trace conditioning has not been considered as having a role in drug conditioning. In several recent reports we have conducted experiments in which we first established a contextual drug CS using a delay conditioning protocol and subsequently used this same CS in a trace drug conditioning protocol with the same or different drug treatment and showed that the CS could be strongly modified by trace conditioning. These observations take on importance in that it has been well established that delay and trace conditioning are mediated by different CNS systems. Delay conditioning is mediated by cerebellar mechanisms, conforming to the general idea of Pavlovian conditioning as a reflexive type of learning whereas trace conditioning involves the hippocampus and frontal cortex brain structures more commonly associated with voluntary behavior. In this proposal we suggest that the emergence of potent drug associations that motivate drug-seeking behavior and addiction are initiated by delay conditioning and subsequently amplified and linked to higher brain functions by trace conditioning.