Response inhibition and psychomotor speed during methadone maintenance: impact of treatment duration, dose, and sleep deprivation.

BACKGROUND: In opiate-dependent individuals, abstinence results in deficits in cognitive functioning, which may be exacerbated by medication-associated sleep disruption. METHOD: To assess cognitive function and the influence of sleep deprivation (SD), 14 healthy control (HC) and 22 methadone maintained (MM) participants completed the continuous performance task (CPT) after a baseline night, a night of total SD, and two recovery sleep nights. The digit symbol substitution task (DSST) was administered at bedtime and in the morning. Secondary analyses separated MM participants into short- (< 12 months; n=8) and long-term (≥ 12 months; n=14) treatment duration groups, and into low- (< 80 mg; n=9) and high-dose (≥ 80 mg; n=13) groups. RESULTS: Linear mixed model ANOVAs revealed that there was no effect of SD. Across all days MM participants had more errors of omission, fewer correct responses, and slower reaction times (RTs) on the CPT, and fewer accurate substitutions on the evening and morning DSST. Short-term MM participants exhibited slower RTs on the CPT, and fewer correct substitutions on the evening DSST compared to long-term MM participants. Low-dose MM participants had slower RTs on the CPT than HCs and high-dose MM participants. CONCLUSION: These data demonstrate that methadone-maintained individuals exhibit poorer performance on tasks of psychomotor speed and selective attention/impulsivity, but with longer-term treatment, performance appears to return toward control levels. Furthermore, while one day of SD was enough to alter subjective reports of sleep quality, cognitive function may be more resilient.

Effects of prenatal cocaine exposure on dopamine system development: a meta-analysis.

Several studies have investigated the effects of prenatal cocaine (PCOC) exposure on the nigrostriatal dopaminergic system in animal models of maternal drug abuse, yet independent examinations of striatal dopamine (DA) receptors and tissue DA levels have produced equivocal results. The current meta-analysis provides a quantitative review of the literature on these topics, and analyzes potential moderators of the effects of PCOC exposure on these variables. The results indicate that the effects of PCOC exposure on striatal DA levels, D1 and D2 receptor-binding densities, and D2 receptor-binding affinity are negligible when collapsed over age, sex, species, and several other methodological variables. However, effects of PCOC exposure on some dopaminergic measures were significantly influenced by factors such as age and sex. As expected, and as suggested by the selectivity and specificity of PCOC-induced changes reported in the published literature, the direction and magnitude of differences between genders or age groups in this study were not systematic across all dependent measures. Generally, PCOC exposure was more often linked to decreases, rather than increases, in the selected dependent measures. These findings indicate that PCOC exposure produces selective alterations in striatal dopaminergic system function which do not appear under all experimental circumstances, but which may be important factors in behavioral alterations seen in selected groups after PCOC exposure.

Prenatal cocaine exposure alters behavioral and neurochemical sensitization to amphetamine in adult rats.

This study examined the neurochemical correlates of amphetamine (AMPH)-induced behavioral effects in prenatally saline (PSAL)-exposed or cocaine (PCOC)-exposed male rats. Pregnant Long-Evans rats received saline or saline containing cocaine hydrochloride (20 mg/kg s.c., b.i.d.) from gestational days 15-21. Animals were left with their biological mothers. Adult offspring were exposed to daily saline or AMPH (0.5, 1.5, or 5 mg/kg, i.p.) injections for 7 days. Behaviors were recorded in an open field during the first hour post-injection. PCOC rats did not exhibit behavioral anomalies during habituation to injection-stress or placement in the open field. PCOC rats displayed significant alterations in stereotyped responses to acute or intermittent exposure to various doses of AMPH. Within 48 h of the final testing day, striatal tissue was obtained from these animals and electrically-evoked [3H]acetylcholine (ACh) release was measured from striatal slices. Superfusion of tissue slices with various concentrations of AMPH (1-1000 nM) produced dose-dependent inhibition of ACh release in both PSAL and PCOC rats repeatedly injected with saline as adults. However, AMPH-induced inhibition of ACh release was decreased in PCOC rats repeatedly injected with AMPH as adults. At 5 mg/kg AMPH, PCOC rats exhibited increased mortality compared to PSAL rats. These data suggest that PCOC exposure produces long-lasting alterations in nigrostriatal transmission and behaviors mediated by this system.

Prenatal cocaine exposure increases serotonergic inhibition of electrically evoked acetylcholine release from rat striatal slices at adulthood.

This study tests the hypothesis that prenatal cocaine (pCOC) exposure (20 mg/kg, bidaily from embryonic days 15-21) modifies 5-HT(3) receptor regulation of electrically-evoked [(3)H]acetylcholine (ACh) overflow from adult male and female (proestrus, diestrus) rat striatal slices. Also, the influence of endogenous dopamine (DA) on serotonin (5-HT) regulation of ACh overflow was determined by assessing the effects alpha-methyl-para-tyrosine (AMPT) pretreatment or sulpiride. Phenylbiguanide (PBG, 5-HT(3) agonist) superfusion dose-dependently inhibited ACh overflow in all groups except the diestrus pCOC group in which there was an enhanced sensitivity to PBG. PBG (10, 30, and 60 microM) produced greater effects in the pCOC male than in the prenatal saline (pSAL) group. The pCOC male group also exhibited greater sensitivity to PBG (30 and 60 microM) than the pCOC proestrus group. PBG inhibition of ACh overflow was comparable in the pSAL male and female (proestrus) groups. PBG inhibition of ACh overflow was greater in the pCOC diestrus group than in the pCOC proestrus (10, 30, and 60 microM), the pSAL diestrus (10 and 30 microM), and the pCOC male (10 microM) conditions. In slices from untreated rats superfused with 30 microM PBG, AMPT pretreatment (68% DA loss) reduced inhibition of ACh overflow, and 1 microM sulpiride increased ACh overflow. ICS205-930 (5-HT(3) antagonist) reduced effectiveness of PBG indicating 5-HT(3) receptor specificity for PBG. In summary, pCOC exposure enhances modulatory effects of 5-HT (via 5-HT(3) receptors) on striatal ACh release in male and females rats and the inhibitory actions of 5-HT(3) receptors are mediated by DA.