Behaviorally conditioned effects of psychoactive drugs in experimental animals: What we have learned from nearly a century of research and what remains to be learned

Continuous treatment with drugs is a crucial requirement for managing various clinical conditions, including chronic pain and neuropsychiatric disorders such as depression or schizophrenia. Associative learning processes, i.e. Pavlovian conditioning, can play an important role for the effects of drugs and could open new avenues for optimizing patient treatment. In this narrative literature review, we summarize available data in experimental animals regarding the behaviorally conditioned effects of psychostimulants such as d-amphetamine and cocaine, the dopamine receptor agonist apomorphine, the dopamine receptor antagonist haloperidol, morphine and antidepressant drugs. In each section, the drug under discussion is briefly introduced, followed by a detailed examination of conditioning features, including doses and dosing regimens, characteristics of the conditioning process such as test environments or specific conditioned stimuli, testing and conditioned response characteristics, possible extinction or reconditioning or reversal training, neural mechanisms, and finally, the potential clinical relevance of the research area related to the drug. We focus on key outcomes, delve into methodical issues, identify gaps in current knowledge, and suggest future research directions.