Behavioral sensitization to psychostimulants and opioids: What is known in rodents and what still needs to be explored in humans?

Repeated exposure to substances of abuse results in an increase in some behavioral responses. This phenomenon, called behavioral sensitization (BS), is well described in preclinical models. However, its existence in humans is still a matter of debate. After a review of preclinical evidence of BS and its mechanisms in animal models, we reviewed the evidence supporting the existence of BS in humans, despite the limited research available in this regard. We focused our review on opioids and psychostimulants, since they share the ability to promote addictive behaviors. Further, they induce BS despite their distinct sedative and stimulant properties. Moreover, we proposed future research perspectives in this review to address the remaining unsolved questions, especially regarding BS in humans using a harm reduction approach.

Chronic exposure to cocaine is associated with persistent behavioral disturbances. A cross-sectional dimensional study in outpatients with multiple substance use disorders.

RATIONALE: Behavioral disturbances (BD) are prevalent in patients with substance use disorders (SUD). OBJECTIVES: To test the hypothesis that chronic exposure to cocaine could favor the acquisition of BD that were not present in childhood. METHODS: We used child and adult ADHD self-report screening scales (WURS-25 and ASRS-6, respectively, with their usual threshold) as assessment tools for significant BD. In a cross-sectional assessment of 382 patients with multiple SUD, we investigated BD and then "de novo" BD (i.e., by restricting the sample to patients below the threshold for childhood BD) (N = 214). We also tested for a gradient effect between patients' lifetime DSM IV cocaine and opioid dependence status and the prevalence of BD. RESULTS: BD were found in 188/382 (42.9%) subjects and in 74/214 (34.6%) subjects. Three clinical factors were associated with BD in the whole sample: the number of cocaine dependence criteria (OR = 1.36 [1.14-1.64], p = 0.001), the number of opioid dependence criteria (OR = 0.69 [0.52-0.91], p = 0.010), and a personal history of using cocaine through rapid routes of administration (OR = 0.41 [0.19-0.88], p = 0.022). The same three factors were associated with "de novo" BD in the restricted sample: OR = 1.35 ([1.11-1.63], p = 0.002), OR = 0.83 ([0.70-0.99], p = 0.046), and OR 0.37 ([0.16-0.86], p = 0.022), respectively. There were significant gradients for BD according to the cocaine exposure categories in the whole (Mantel-Haenszel, p < 0.001) and in the restricted sample (Mantel-Haenszel, p = 0.002). CONCLUSIONS: Cocaine exposure was positively associated with behavioral disturbances in a dose-dependent manner in this clinical sample, whilst opioid exposure showed a negative association.