ABSTRACT
BACKGROUND: Reduced metabolic activity in frontal brain regions, and reduced striatal dopamine receptor densities have been shown in alcohol dependent patients. Little is known on functional changes in the fronto-striatal-thalamic dopaminergic neurocircuitry in these patients. The objective of this study was to assess sensitivity of prefrontal dopamine receptors in alcohol dependent patients. EXPERIMENTAL PROCEDURES: Male alcohol dependent patients (N=40) and healthy controls (N=39) performed an AX-continuous performance test before and after administration of the DA agonist apomorphine (0.005 mg/kg). RESULTS: At baseline alcohol dependent patients were slower and less accurate compared to healthy controls. After administration of apomorphine, performance improved in alcohol dependent patients and deteriorated in healthy controls. CONCLUSIONS: Reduced cognitive performance in alcohol dependent patients compared with healthy controls may indicate dopamine dysfunctioning at the prefrontal level. Improvement of cognitive performance in alcohol dependent patients after administration of apomorphine and deterioration in healthy controls provides evidence for an inverted U-shape relation between dopaminergic functioning and cognitive performance.
Subject(s)
Alcoholism/psychology , Apomorphine/pharmacology , Cognition/drug effects , Dopamine Agonists/pharmacology , Psychomotor Performance/drug effects , Adult , Alcoholism/complications , Diagnosis, Dual (Psychiatry) , Dopamine/metabolism , Female , Humans , Male , Mental Disorders/complications , Mental Disorders/psychology , Middle Aged , Reaction Time/drug effects , Receptors, Dopamine/drug effects , Socioeconomic FactorsABSTRACT
RATIONALE: Sedation following antihistamine use poses a danger to ambulant patients involved in daily activities such as driving. OBJECTIVE: To investigate effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on driving ability during normal traffic. METHODS: Forty-eight healthy volunteers participated in a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3 and 4, exactly 1.5 h before the start of the standardized driving test (performed on day 1 and day 4). In the standardized driving test, subjects were instructed to drive with a steady lateral position, while maintaining a constant speed (95 km/h). Primary parameter was the standard deviation of lateral position (SDLP; cm). Statistical analyses were performed separately for day 1 and day 4, using analysis of variance and an equivalence test. Equivalence to placebo was evidenced if the 95% confidence interval lay between -2.6 cm and +2.6 cm. RESULTS: SDLP after levocetirizine was equivalent to placebo on both day 1 (-0.66 cm; +1.12 cm) and day 4 (-0.37 cm; +1.28 cm). In contrast, SDLP after diphenhydramine differed significantly from placebo on both day 1 ( P<0.0001) and day 4 ( P<0.0003). On day 1, the 95% confidence interval of diphenhydramine (+1.85 cm; +3.63 cm) was partially above the upper equivalence limit (+2.6 cm), indicating clinically relevant driving impairment. On day 4, however, the 95% confidence interval of diphenhydramine (+0.74 cm; +2.38 cm) was contained within the acceptance range. CONCLUSION: In contrast to diphenhydramine, driving performance was not significantly affected while using 5 mg levocetirizine once daily.
Subject(s)
Automobile Driving , Cetirizine/adverse effects , Diphenhydramine/adverse effects , Histamine H1 Antagonists/adverse effects , Piperazines/adverse effects , Adult , Cetirizine/administration & dosage , Diphenhydramine/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Female , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Male , Piperazines/administration & dosageABSTRACT
BACKGROUND: Central nervous system adverse effects, such as sedation, often accompany the use of first-generation antihistamines. These effects might interfere with memory functioning and psychomotor performance. Levocetirizine was recently introduced as a new antihistamine said to be free from sedative effects. OBJECTIVE: We sought to investigate the effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on memory and psychomotor performance after acute (day 1) and subchronic (day 4) daily administration in 48 healthy volunteers (24 men and 24 women). METHODS: This study was a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3, and 4, 3 hours before the start of the laboratory test battery (performed on days 1 and 4), comprising a word-learning test, the Sternberg Memory Scanning Test, a tracking test (easy and hard version), and a divided attention test (tracking and memory scanning simultaneously). Statistical analyses were performed separately for days 1 and 4 by using analysis of variance. RESULTS: On day 1, diphenhydramine significantly impaired tracking performance (easy: F(1,90) = 25.9, P <.0001; hard: F(1,90) = 20.5, P <.0001) and divided attention (tracking: F(1,90) = 23.8, P <.0001; memory scanning: F(1,90) = 22.0, P <.0001). Results on word-learning tests and Sternberg Memory Scanning Tests were not significantly impaired. On day 4, the effects of diphenhydramine did not reach significance. In contrast, on both days 1 and 4, levocetirizine did not significantly impair laboratory test performance. CONCLUSION: The results show that memory, attention, and tracking performance are unaffected after acute and subchronic administration of levocetirizine (5 mg), whereas diphenhydramine (50 mg) significantly affected divided attention and tracking after acute administration.
