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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.

Rationale: Chronic administration of morphine induces adaptations in neurotransmission system such as the dopamine pathway, and these modifications could be influenced by the drug administration pattern. Methadone and buprenorphine are the two main opioid substitution therapies, and despite their protracted use in humans, no study has investigated their ability to regulate dopamine system after chronic exposure/withdrawal., Objectives: We evaluated the consequences of two administration patterns of methadone and buprenorphine on striatal dopamine D1 (D1R) and D2 (D2R) receptor levels., Methods: Mice were treated with escalating doses of methadone or buprenorphine for 5 days either once daily (binge) or three times a day (TTD). D1R and D2R density in striatum was measured by autoradiography using [(3)H]-SCH23390 and [(3)H]-raclopride, respectively, at 1 (WD1), 14 (WD14), and 35 (WD35) days after the last opioid injection., Results: A downregulation of D1R was observed upon TTD administration of buprenorphine and binge methadone treatment while an increase of those receptor levels was detected both with binge buprenorphine and TTD methadone treatments. Concerning the D2R, we rather measured an early or late downregulation with both agonists and administration patterns., Conclusions: Our results demonstrated that methadone and buprenorphine were able to differentially regulate dopamine receptor density depending on the withdrawal period and the administration pattern.

Rationale: Chronic exposure to drugs of abuse induces important modifications on neuronal systems. Increasing evidence shows that the consequences to chronic cocaine exposure can be different depending on the administration pattern., Objectives: The aim of the present study was to evaluate the consequences of two cocaine administration patterns on dopaminergic receptor regulation., Methods: Male Sprague-Dawley rats were injected with cocaine (20 mg/kg, i.p.) for 14 days according to an intermittent (one daily injection) or a binge (three daily injections) pattern. By autoradiography, we compared the modifications of dopamine D1 and D2 receptor densities in the dopaminergic systems (mesocorticolimbic and nigrostriatal) 1 (WD1) and 14 (WD14) days after the last cocaine injection., Results: On WD1, we observed modifications of D1 receptors after the binge cocaine treatment pattern while no modification was observed after the intermittent pattern, suggesting that multiple daily injections are needed to induce early D1 receptor modifications. On the contrary, densities of the D2 receptors were modified by both cocaine administration patterns, and interestingly, they were opposite depending on the administration pattern. On WD14, we observed different modifications of D1 and D2 receptors depending on the administration pattern, suggesting that the cocaine administration pattern promoted long-term regulations of the dopaminergic system., Conclusion: Two cocaine administration patterns induce different modifications of the dopaminergic receptor densities.

Rationale: Behavioral sensitization induced by repeated morphine administrations may depend on patterns of administration. However, neurobiological mechanisms involved in this sensitization are largely unknown., Objectives: We compared the effects of intermittent (20 mg/kg, once daily for 7 days) and chronic (escalating doses from 5 to 40 mg/kg, three times a day for 5 days) morphine treatments in mice on locomotor activity. We also quantified, by autoradiography, mu opioid receptor (MOR) in ventral tegmental area (VTA), dopamine D1 (D1R) and D2 (D2R) receptors in striatum., Results: Whereas the intermittent treatment led to a long-term sensitization to locomotor effects of morphine [until withdrawal day (WD) 14], the chronic treatment induced a tolerance (WD1) followed by a transient sensitization (WD14). Binding studies demonstrated a decrease of MOR in VTA at WD1 for the chronic treatment. In contrast, striatal D1R level was decreased at WD1, and increased at WD14 for the chronic treatment. For the D2R, we observed a decrease from WD1 to WD14 for the intermittent treatment and an increase at WD1 followed by a decrease at WD14 for the chronic treatment., Conclusions: These results demonstrate that chronic and intermittent morphine treatments could induce different behavioral adaptations that could be explained in part by distinct changes occurring in dopamine and opioid systems.