Assessments of the Effects of Nicotine and Ketamine Using Tyrosine Hydroxylase-Green Fluorescent Protein Transgenic Zebrafish as Biosensors.

Assessments of the effects of nicotine and ketamine using tyrosine hydroxylase-green fluorescent protein transgenic zebrafish as biosensors.

Filed under: Addiction Rehab

Biosens Bioelectron. 2012 Oct 12; 42C: 177-185
Suen MF, Chan WS, Hung KW, Chen YF, Mo ZX, Yung KK

Transgenic zebrafish are a common vertebrate model system for the study of addictive behavior. In the present study, plasmid constructs containing green fluorescent protein (GFP) and the promoter of tyrosine hydroxylase (TH), a key synthetic enzyme for catecholamines, were produced. The TH-GFP constructs were microinjected into zebrafish embryonic cells. Three days post-fertilization, GFP began expressing in distinct catecholaminergic areas. The TH-GFP transgenic zebrafish were employed as live biosensors to test the effects of the commonly abused drugs nicotine and ketamine. First, locomotion assays were used to study the general excitatory effects of the drugs. Maximal locomotor activity was obtained after treatment with a high concentration of nicotine (10?M), but with a much lower concentration of ketamine (0.1?M). Second, TH protein levels in zebrafish brains were assessed by Western blot. TH protein levels were significantly increased, with maximal protein levels found after treatment with the same drug concentrations that gave maximal locomotor activity. Importantly, analysis of GFP in the zebrafish catecholaminergic areas revealed the same expression patterns as was obtained by Western blot. The present results indicate that increased locomotor activity can be correlated to TH protein expression, as indicated by Western blot and expression of TH-GFP. We have shown that TH-GFP expression is a reliable method to show the effects of drugs on TH expression that may be employed as a novel high-throughput live biosensor for screening drugs of abuse.
HubMed – addiction


Driver anger on the information superhighway: A content analysis of online complaints of offensive driver behaviour.

Filed under: Addiction Rehab

Accid Anal Prev. 2012 Nov 28; 51C: 84-92
Wickens CM, Wiesenthal DL, Hall A, Roseborough JE

In recent years, several websites have been developed allowing drivers to post their complaints about other motorists online. These websites allow drivers to describe the nature of the offensive behaviour and to identify the offending motorist by vehicle type, colour, and license plate number. Some websites also ask drivers to list the location where the event took place and the exact date and time of the offence. The current study was a content analysis of complaints posted to between 1999 and 2007 (N=5624). The purpose of the study was to: (1) assess the research value of this novel data source; (2) demonstrate the value of content analysis to the study of driver behaviour; (3) further validate an existing coding scheme; (4) determine whether this new data source would replicate previous research findings regarding the most frequent types of driver complaints and temporal distribution of these reports; (5) provide recommendations for improved driver training and public safety initiatives based on these data. A coding scheme that was originally developed for an assessment of complaints submitted to the Ontario Provincial Police (OPP) (Wickens et al., 2005) was revised to accommodate the new dataset. The inter-rater reliability of the revised coding scheme as applied to the website complaints was very good (kappa=.85). The most frequently reported improper driver behaviours were cutting/weaving, speeding, perceived displays of hostility, and tailgating. Reports were most frequent on weekdays and during the morning and afternoon rush hour. The current study replicated several findings from the analysis of reports to the OPP, but possible differences in the sample and data collection method also produced some differences in findings. The value of content analysis to driver behaviour research and of driver complaint websites as a data source was demonstrated. Implications for driver safety initiatives and future research will be discussed.
HubMed – addiction


Antagonizing 5-HT(2A) receptors (M100907) and stimulating 5-HT(2C) receptors (Ro60-0175) blocks cocaine-induced locomotion and zif268 mRNA expression in Sprague-Dawley rats.

Filed under: Addiction Rehab

Behav Brain Res. 2012 Nov 28;
Burton CL, Rizos Z, Diwan M, Nobrega JN, Fletcher PJ

Serotonin (5-HT) plays a role in several psychiatric disorders including drug addiction. The 5-HT system modulates the activity of midbrain dopamine (DA) systems, and the behavioural effects of psychostimulants mediated by these systems. The direction of this modulation depends upon the 5-HT receptor subtypes involved, with 5-HT(2A) and 5-HT(2C) receptors having opposing effects. For example the 5-HT(2A) receptor antagonist M100907 and the 5-HT(2C) receptor agonist Ro60-0175 both attenuate several cocaine-induced behavioural and neurochemical effects. To investigate the possible brain regions involved in the interactions between 5-HT(2A) or 5-HT(2C) receptor ligands and cocaine-induced behaviour, we examined the effects M100907 or Ro60-0175 on cocaine-induced locomotion and mRNA expression of the immediate early gene zif268. Sprague-Dawley rats were pre-treated with M100907 (0.5mg/kg), Ro60-0175 (1.0mg/kg) or vehicle, and then injected with cocaine (15mg/kg) or vehicle. Locomotor activity was monitored for 60min before rats were sacrificed for zif268 mRNA in situ hybridization mapping. Cocaine increased locomotor activity and zif268 mRNA expression consistently in the nucleus accumbens core, the orbitofrontal cortex and in the caudate. M100907 attenuated cocaine-induced locomotion and zif268 mRNA expression in these brain regions in a defined subset of rats but failed to alter any effects of cocaine in another defined subset of rats. Ro60-0175 blocked cocaine-induced locomotion and zif268 mRNA expression in similar brain regions. Our results suggest that despite the opposing actions of 5-HT at 5-HT(2A) and 5-HT(2C) receptors, ligands acting on these receptors likely modulate cocaine-induced locomotion via a common mechanism to influence DA-dependent circuitry.
HubMed – addiction


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