Oral methylphenidate establishes a conditioned place preference in rats

Emerging data suggest that illicit methylphenidate abuse is a growing problem. Although abuse of the drug typically occurs by the intranasal route, oral (per os; p.o.) methylphenidate also has abuse potential. The present study compared the effects of p.o. and intraperitoneal (i.p.) methylphenidate in rats using the conditioned place preference (CPP) procedure. Young adult male Sprague-Dawley rats were trained to consume oyster crackers injected initially with saline. Next, rats were randomly assigned to receive p.o. or i.p. methylphenidate (3 or 10mg/kg) or saline immediately or 30min prior to 30min conditioning trials. Methylphenidate or saline were each paired 4 times with an end compartment; preference for the methylphenidate-paired compartment was then assessed on a drug-free session. When given immediately prior to conditioning, significant CPP was obtained with both 3 and 10mg/kg of i.p. methylphenidate, but only with 10mg/kg of p.o. methylphenidate. When given 30min prior to conditioning, there was no evidence of CPP for any dose of i.p. or p.o. methylphenidate. These findings are the first demonstration that p.o. methylphenidate has rewarding effects, although i.p. methylphenidate is obtained at a 3mg/kg dose which did not establish CPP with p.o. administration. The lack of CPP following 30min pretreatment also suggests that conditioning may require the CS to be associated with a US of ascending, rather than descending, brain levels of methylphenidate. These results are consistent with clinical evidence of the reduced abuse liability of p.o. methylphenidate relative to methylphenidate taken by other (e.g., intranasal) routes.     

Methylphenidate normalizes elevated dopamine transporter densities in an animal model of the attention-deficit/hyperactivity disorder combined type,but not to the same extent in one of the attention-deficit/hyperactivity disorder inattentive type

The spontaneously hypertensive rat (SHR/NCrl) is a validated model of attention-deficit/hyperactivity disorder (ADHD) combined subtype, whereas a recently identified substrain of the Wistar Kyoto rat (WKY/NCrl) is a model of ADHD inattentive subtype. In this study, we first examined the expression of genes involved in dopamine signaling and metabolism in the dorsal striatum and ventral mesencephalon of these two rat strains, as well as three reference control strains (WKY/NHsd, WK/HanTac, and SD/NTac) using quantitative real time RT-PCR. Next, striatal dopamine transporter (DAT) density was determined by ligand binding assay in the two ADHD-like strains at different developmental stages and after methylphenidate treatment. In adult rats, the mRNA expression of DAT and tyrosine hydroxylase was elevated in SHR/NCrl and WKY/NCrl rats compared to control strains, with differences between SHR/NCrl and WKY/NCrl rats also evident. During normal development, changes of striatal DAT densities occurred in both strains with lower densities in WKY/NCrl compared to SHR/NCrl after day 25. Two-weeks methylphenidate treatment during different developmental stages was associated with decreased striatal DAT density in both rat strains compared to the non-treated rats with more pronounced effects followed prepubertal treatment. These results suggest differences in the pathophysiology of the combined versus the predominantly inattentive animal model of ADHD. Finally, treatment with methylphenidate might reduce elevated DAT levels more effectively in the combined subtype especially when applied before puberty.     

Effects of sex hormones on associative learning in spontaneously hypertensive rats

Pavlovian conditioning of a visual stimulus paired with food was examined in spontaneously hypertensive rats (SHR), which are a commonly used model for Attention-Deficit/Hyperactivity Disorder (ADHD), and in Wistar rats (normoactive control). In gonadally intact rats of both strains, males spent more time in the food cup following onset of the light than did females, indicating a stronger association of the conditioned stimulus (CS) with reward. Gonadectomy carried out in adulthood affected conditioning differently in the two strains. In Wistar rats, gonadectomy had no effect on conditioned responding in females, but reduced conditioned responding in males, effectively eliminating the sex difference in behavior. This result suggests that circulating androgens in male Wistar rats normally aid conditioning in this task. In contrast, gonadectomy enhanced conditioning in both sexes in the SHR rats, indicating that androgens and/or estrogens impair conditioned associations in this strain. These data indicate that gonadal steroids can influence conditioning in rats and that the valence of steroid action on this behavior is strain-dependent. To the extent that SHR serves as a model of ADHD in humans, the influence of steroids on associative learning may play a role in the expression of ADHD-like behaviors.     

Wistar Kyoto and Wistar rats differ in the affective and locomotor effects of nicotine

Anhedonia is a characteristic of clinical depression and has been associated with dysfunction of the mesolimbic dopaminergic system, a system also involved in mediating nicotine reward. To further examine the relationship between anhedonia, clinical depression and nicotine reward, the present experiment determined if Wistar Kyoto (WKY) rats, an animal model of clinical depression, differed from Wistar rats in nicotine conditioned place preference (CPP). Strain differences in nicotine-induced changes in locomotor activity also were determined simultaneously. To determine if strain differences were specific to reward-based learning, nicotine or lithium chloride (LiCl) conditioned taste avoidance (CTA) experiments were conducted. Rats received vehicle or nicotine (0.4 or 0.8 mg/kg) during a multi-trial, biased CPP training procedure or received vehicle, nicotine (0.2, 0.4 or 0.8 mg/kg) or lithium chloride (LiCl; 0.0375, 0.075 or 0.15 M) during a multi-trial CTA training procedure. Whereas both nicotine doses (0.4 and 0.8 mg/kg) initially induced hypoactivity, only the moderate nicotine dose (0.4 mg/kg) induced hyperactivity with repeated administration and produced a CPP in Wistar rats. Both nicotine doses failed to alter locomotor activity or produce a CPP in WKY rats. WKY rats also acquired a LiCl CTA more slowly and less robustly compared to Wistar rats. In contrast, nicotine dose-dependently produced a CTA in both strains and WKY rats were more sensitive to the avoidance effects of nicotine compared to Wistar rats. Collectively, these results suggest that WKY rats show deficits in nicotine reward and specific aversive drug stimuli compared to Wistar rats.     

Effects of methylphenidate on saccadic responses in patients with ADHD

This study examined the effects of methylphenidate on different measures of saccade control, using a repeated measurement design, and the experimental and statistical control of practice effects. Twenty-seven boys with ADHD (mean age 12.6 years, range 10-15 years) were randomly assigned to two testing order conditions (first on-, second off-medication versus first off-, second on-medication) and accomplished the pro-saccadic overlap and the anti-saccadic 200-ms gap tasks (200 trials each). Methylphenidate was found to reduce pro- and anti-saccadic reaction times, error correction times, and the proportion of direction errors during the anti-saccade task. Furthermore, the drug augmented the proportions of express saccades and error corrections. Overlain practice effects were found for most of these measures. Our results suggest a weakening of the fixation, and a strengthening of the "voluntary" system of saccade control by methylphenidate.     

Treatment with a serotonin-depleting regimen of MDMA prevents conditioned place preference to sex in male rats

Among young adults, 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular drug of abuse, and anecdotal evidence indicates that repeated use of MDMA may result in impairments in sexual function and decreased sex drive in human users. There has been little investigation of the effects of MDMA on sexual function in rodents. In the present study, the authors determined that in male rats (Rattus novegicus) tested in a sexually na?ve or a sexually experienced state, administration of a serotonin (5-HT)-depleting regimen of MDMA did not produce a change in mount, intromission, and ejaculation latency or in mount and intromission frequency compared with such latency and frequency in vehicle-treated control rats. In contrast to vehicle-treated rats, MDMA-treated rats did not form a conditioned place preference (CPP) to sex. Failure of MDMA-treated rats to form CPP to sex may be due to MDMA-induced impairments in circuits mediating sexual reward.     

Increased Locomotor Activity and Non-Selective Attention and Impaired Learning Ability in SD Rats after Lentiviral Vector-Mediated RNA Interference of Homer 1a in the Brain

Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.     

Abnormal topography and altered acquisition of conditioned eyeblink responses in a rodent model of attention-deficit/hyperactivity disorder

The spontaneously hypertensive rat (SHR) has been suggested as a possible animal model of attention-deficit/hyperactivity disorder (ADHD). Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in ADHD, prompting investigation into whether SHRs also exhibit eyeblink conditioning impairments. In Experiment 1, SHRs and a control strain, Wistar, were trained on a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). SHRs exhibited faster acquisition of eyeblink conditioned responses (CRs) and displayed mistimed (early onset and peak latency) and larger CRs in comparison with Wistar rats. In subsequent extinction training, SHRs were slower to extinguish CRs. The authors conducted Experiment 2 using separate rats to rule out the possibility that the results of Experiment 1 were due to nonassociative responding. SHRs and Wistar rats were presented with explicitly unpaired tone and periorbital stimulation stimuli. There was no evidence of conditioning in either group, nor were there differences between the groups in terms of the number of eyeblink responses elicited by the tone. The current results support the hypothesis of cerebellar abnormalities in this rodent model of ADHD.     

Interaction between behavioral despair and addictive behaviors in rats

It has been suggested that depression can be either a cause or a consequence of drug abuse, providing a possible explanation for the fact that the prevalence of depression is almost 3-fold higher in drug abusers than in the general population. However, the interaction between depression and drug abuse has not been fully elucidated. To examine the interaction between behavioral despair and addictive behaviors, we used the Porsolt's forced swim test (FST) as a model of behavioral despair, and we used morphine conditioned place preference (CPP) and repeated morphine exposure as models of addictive behaviors. We found that rats exposed to a standard FST (15 min on day 0 training) rather than a weak FST (10 min on day 0 training) exhibited behavioral despair, which selectively potentiated morphine CPP (mCPP) but not food CPP (fCPP). The antidepressant imipramine (15 mg/kg, i.p.), which blocked the behavioral despair, prevented the standard FST potentiated morphine CPP. Conversely, repeated exposure to morphine (10 mg/kg, s.c.) for 6, 12 or 20 days decreased, had no effect on, or increased the immobility time, respectively, in the subsequent standard FST. Furthermore, repeated morphine exposure for 20 days exacerbated the pre-existing behavioral despair. Thus, our findings suggest that behavioral despair may increase the vulnerability of individuals to opiate abuse, which may in turn enhance behavioral despair.     

Efficacy of methylphenidate, psychosocial treatments and their combination in school-aged children with ADHD: a meta-analysis

Introduction

This meta-analysis compares effect-sizes of methylphenidate and psychosocial treatments and their combination on ADHD, concurrent oppositional, conduct symptoms, social behaviors and academic functioning.

Method

Several databases (PubMed, PsycInfo, ISI Web of Science) were searched for articles published between 1985 and September 2006. Inclusion criteria were: a diagnosis of ADHD; age from 6–12 years; a randomized controlled treatment design; efficacy established with parent and teacher rating scales; psychosocial treatments used were described as behavioral or cognitive-behavioral; the methylphenidate treatment was short-acting; and finally, treatment was conducted in a clinical setting.

Results

ADHD outcomes showed large mean weighted effect-sizes for both methylphenidate and combined treatments, psychosocial treatments had a moderate mean weighted effect-size; a similar pattern emerged for oppositional and conducted behavior symptoms. Social behavior outcomes showed comparable moderate mean weighted effect-sizes for all treatments, while on academic functioning, all treatments had low mean weighted effect-sizes. There was no correlation between duration of psychosocial treatment and effect-size.

Conclusions

Both methylphenidate and psychosocial treatments are effective in reducing ADHD symptoms. However, psychosocial treatment yields smaller effects than both other treatment conditions. Psychosocial treatment has no additional value to methylphenidate for the reduction of ADHD and teacher rated ODD symptoms. However, for social behavior and parent rated ODD the three treatments were equally effective. For improvement of academic functioning no treatment was effective.     

A comparative study of the effects of ABT-418 and methylphenidate on spatial memory in an animal model of ADHD

Impaired learning performance in scholastic settings is a characteristic of attention deficit hyperactivity disorder (ADHD). Our present study compares the effect of a nicotinic acetylcholine receptor (nAChR) agonist, ABT-418, and methylphenidate (MPH) on spatial memory in spontaneously hypertensive rats (SHRs), an animal model of ADHD. Neither chronic administration of ABT-418 nor MPH affected the learning performance during training in the Morris water maze. However, both compounds significantly improved memory. SHRs treated with a combination of the compounds did not perform better than either drug alone. Furthermore, the cortical α4 and β2 nAChR subunits and the hippocampal α4 subunit expression were significantly enhanced by ABT-418 treatments. Collectively, these results suggest that ABT-418 effectively improved spatial memory in an animal model of ADHD, providing a theoretical foundation for the use of a nAChR agonist in ADHD treatment.     

Ethanol-induced delta-opioid receptor modulation of glutamate synaptic transmission and conditioned place preference in central amygdala

Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors play an essential role in drug reward and dependence for many drugs of abuse including alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely unknown at present. Previous animal studies using systemic approaches with DOR antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease, an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR inhibition or deletion. In the present study, we used ethanol-conditioned rats to investigate adaptive DOR function in neurons of the central nucleus of the amygdala (CeA), a key brain site for alcohol reward and addiction. We found that functional DOR was absent in glutamate synapses of CeA neurons from control rats, but it emerged and inhibited glutamate synaptic currents in CeA neurons from rats displaying ethanol-induced behavior of conditioned place preference (CPP). Analysis of paired-pulse ratios and miniature glutamate synaptic currents revealed that the recruited DOR was present on glutamatergic presynaptic terminals. Similar induction of functional DOR was also found on GABA synapses. Furthermore, microinjection of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo. These results suggest that repeated alcohol exposure recruits new functional DOR on CeA glutamate and GABA synapses, which may be involved in the expression or maintenance of ethanol-induced CPP behavior.     

Valproic acid sodium inhibits the morphine-induced conditioned place preference in the central nervous system of rats

The present study was performed to investigate the effects of valproic acid sodium (VPA), a widely utilized antiepileptic drug, on the establishment of chronic morphine-induced conditioned place preference (CPP). The rat model of morphine-induced CPP was conditioned with alternating intracerebroventricular (i.c.v.) injections of morphine (60 microg/6 microl) and saline for 5 days. To investigate the influence of VPA on morphine-induced CPP, rats received chronic pretreatment of i.c.v. VPA (500 microg/rat) 10 min previous to the daily morphine injection. The results demonstrated that the morphine-induced CPP was significantly attenuated by VPA pretreatment, while the VPA itself could not induce any CPP or conditioned place aversion (CPA) effects. The results of the present study not only confirmed the reliability of establishing morphine-induced CPP model by i.c.v. injection, but also suggest that the antiepileptic drug VPA may be utilized as potential therapeutic medications for drug abuse in the future.     

Absence of association with DAT1 polymorphism and response to methylphenidate in a sample of adults with ADHD.

A polymorphism in the dopamine transporter gene (DAT1) has been previously associated with ADHD and methylphenidate has been hypothesized to block the dopamine transporter. The goal of this study was to examine whether a 40-bp variable number of tandem repeats (VNTR) of DAT1 moderate response and adverse effects associated with methylphenidate treatment of adults with ADHD. Subjects were 106 adults with ADHD enrolled in 6-week randomized placebo-controlled parallel design trials of methylphenidate (OROS and immediate release preparations). There was no evidence of an association between DAT1 VNTR and response to methylphenidate (F(2,100) = 0.04, P = 0.9). Similarly, there was no pattern of statistically significant association with DAT1 VNTR and cardiovascular or spontaneously reported adverse effects. We failed to identify an association with DAT1 and the response or tolerability of methylphenidate in adults with ADHD.     

Effects of atomoxetine and methylphenidate on sleep in children with ADHD

STUDY OBJECTIVES: This study compared the effects of atomoxetine and methylphenidate on the sleep of children with attention-deficit/hyperactivity disorder (ADHD). This study also compared the efficacy of these medications for treating ADHD in these children. DESIGN: Randomized, double-blind, crossover trial. SETTING: Two sleep disorders centers in the United States; 1 in a private-practice setting and 1 in a hospital setting. PATIENTS: 85 children diagnosed with ADHD. INTERVENTIONS: Twice-daily atomoxetine and thrice-daily methylphenidate, each for approximately 7 weeks. MEASUREMENTS AND RESULTS: Relative to baseline, the actigraphy data indicated that methylphenidate increased sleep-onset latency significantly more than did atomoxetine (39.2 vs 12.1 minutes, p < .001). These results were consistent with the polysomnography data. Child diaries indicated that it was easier to get up in the morning, it took less time to fall asleep, and the children slept better with atomoxetine, compared with methylphenidate. Parents reported that it was less difficult getting their children up and getting them ready in the morning and that the children were less irritable, had less difficulty getting ready for bed, and had less difficulty falling asleep with atomoxetine, compared with methylphenidate. There were no significant differences between medications using the main measures of efficacy for ADHD treatment. Atomoxetine was superior on some secondary ADHD treatment-efficacy measures, based on parent reports. The only significant differences in treatment-emergent adverse events were greater incidence of decreased appetite and greater incidence of insomnia with methylphenidate. CONCLUSIONS: Patients receiving twice-daily atomoxetine had shorter sleep-onset latencies, relative to thrice-daily methylphenidate, based on objective actigraphy and polysomnography data. Although both medications decreased nighttime awakenings, the decrease was greater for methylphenidate.     

Characterization of dopamine-dependent rewarding and locomotor stimulant effects of intravenously-administered methylphenidate in rats

In general, psychostimulants are thought to exert rewarding and locomotor stimulating effects via increased dopamine transmission in the ventral striatum. However, little is known about the mechanisms underlying the effects of the stimulant drug methylphenidate. The present study examined the putative role of dopaminergic transmission in i.v. methylphenidate reward as measured by conditioned place preference. Rats were shown to exhibit conditioned place preference for i.v. methylphenidate (5 mg/kg, not 2 mg/kg). Administration of the dopamine receptor antagonist cis-flupenthixol (0.1-0.8 mg/kg i.p.), either during conditioning or on test day, dose-dependently attenuated the magnitude of the conditioned place preference. Finally, we examined the effects of bilateral 6-hydroxydopamine lesions of nucleus accumbens core, medial shell or anteromedial olfactory tubercle on the rewarding and locomotor stimulant effects of methylphenidate. Residual dopamine innervation, as assessed by radioligand binding to the dopamine transporter, revealed a significant association between core dopamine innervation and the locomotor stimulant effect of methylphenidate. However, neither core nor medial shell dopamine innervation was related to conditioned place preference magnitude. Instead, conditioned place preference magnitude was associated with dopamine innervation in the anteromedial olfactory tubercle. These results establish a role for dopaminergic transmission in both i.v. methylphenidate conditioned place preference and locomotor stimulation. As well, they suggest that different ventral striatal subregions mediate the rewarding (anteromedial olfactory tubercle) and locomotor stimulant (accumbens core) effects of methylphenidate.     

哌甲酯控释剂治疗对注意缺陷多动障碍儿童父母压力的影响

目的:探讨哌甲酯控释剂(OROS-MPH)治疗对注意缺陷多动障碍(attention deficit hyper-activity disorder,ADHD)患者临床症状和父母压力的影响。方法:采用自身对照研究设计,对符合美国精神障碍诊断与统计手册第四版(Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition,DSM-IV)诊断标准的73名ADHD患者(年龄6~15岁),使用哌甲酯控释剂(18~54mg/d)治疗8周。以父母填写的IOWA Conners量表及研究者填写的ADHD症状评定问卷评估患者的临床症状,并作为主要临床疗效评价指标,以父母填写的父母压力指数量表(Parenting Stress Index,PSI)来评估父母的压力,分别在基线、治疗4周末和8周末用以上问卷进行评估。结果:66名ADHD患儿完成了8周的治疗。经哌甲酯控释剂治疗后,ADHD患者IOWA Conners量表中的注意缺陷/多动因子分、对立/违抗因子分和总分随治疗时间下降(均P<0.001);ADHD症状评定问卷的注意缺陷因子分、多动冲动因子分和总分较服药前下降(均P<0.001);PSI量表的压力总分随时间明显下降(P<0.01),PSI量表中儿童方面分量表中,适应性、父母的接受度、要求、心境、注意不能/多动、父母的强制性6个因子得分均随着时间下降(均P<0.01);在父母方面分量表中,抑郁、角色的限制、配偶关系、孤独、健康状况5个因子得分均随着时间显著下降(均P<0.01)。基线时PSI总分与IOWA Conners量表总分、ADHD症状评定问卷总分呈正相关(r=0.346~0.902,均P<0.01)。结论:哌甲酯控释剂治疗能有效改善ADHD患者的临床症状和改善患者及其父母的压力,提高社会功能。     

Effects of methylphenidate on aggressive urban children with attention deficit hyperactivity disorder

Determined the efficacy of methylphenidate (MPH) in a clinical population of aggressive, urban children diagnosed with attention deficit hyperactivity disorder (ADHD). In previous studies of prepubertal children with ADHD, MPH has been shown to be effective when compared with placebo. Eighteen inner-city children (ages 6 to 12 years), diagnosed with ADHD and attending a summer treatment program for youth with disruptive behavior disorders, participated in a double-blind placebo trial with assessment data obtained from staff in the program and parents at home. Based on staff ratings of the children's behavior in the program and an academic classroom, the children displayed significant improvements in ADHD symptoms and aggressive behavior with low- and high-dose MPH conditions. At home, parents and guardians reported few significant differences between placebo and MPH on behavior ratings. In both settings, MPH was well tolerated with few side effects found during active drug conditions.     

Rewarding property of nicotine and methamphetamine tested by conditioned place preference in rats: effect of chronic nicotine pretreatment

Nicotine is classified as a dependence-producing drug. This study investigated the rewarding property of nicotine employing the conditioned place preference (CPP) paradigm in a three-compartment box, and compared it with that of methamphetamine (MAP). In place conditioning using a biased method, rats were placed in one (white or black) compartment under the drug treatment and placed in the other compartment without drug. In the preference test conducted after conditioning, the time spent in the nicotine-paired compartment significantly increased compared with that in the baseline test, suggesting nicotine's rewarding property, although the property was weaker compared with that of MAP. Chronic nicotine pretreatment by a subcutaneous osmotic mini-pump for 7days before place conditioning tended to increase the rewarding property of nicotine, and the possible mechanism of this effect was discussed.     

A naturalistic study of the effects of pharmacotherapy on substance use disorders among ADHD adults

BACKGROUND: Studies of adults with attention deficit hyperactivity disorder (ADHD) show an elevated prevalence of substance use disorders (SUDs) and the substance abuse literature shows that ADHD is elevated in substance users. Some researchers postulate that stimulant treatment of ADHD increases the risk for SUD in ADHD patients but follow-up studies suggest treatment protects patients from subsequent SUDs. This report uses retrospective data to assess the impact of prior ADHD pharmacotherapy on SUDs in 206 ADHD adults (n=79 late-onset ADHD, n=127 full ADHD) grouped by lifetime history of ADHD treatment (no treatment, past treatment, current and past treatment). METHOD: Structured Clinical Interview for DSM-IV (SCID) data were used to establish abuse and dependence, and Drug Use Screening Inventory (DUSI) responses were used to establish prevalence of use, preference for cigarettes, alcohol and drugs of abuse, complications from use, and motivation for use (get high, change mood, sleep better). RESULTS: No differences were found in the prevalence of cigarette smoking, alcohol or drug abuse or dependence, as well as no significant differences in 1-month prevalence of any use or use more than 20 times. No differences were found in complications of drug or alcohol use across groups. Subjects with current treatment rated getting high as a motivating factor significantly more frequently than subjects in the past treatment group; this result lost significance when we included ADHD diagnostic category. CONCLUSIONS: Our results are consistent across substances and ADHD diagnoses, and support the hypothesis that pharmacotherapy does not cause subsequent SUDs.