Chris Chandler

Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: the saga continues...

Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: the saga continues . . .

Influence of Sex and Female Hormones on Nicotine-Induced Changes in Locomotor Activity in Rats

The acute and chronic effects of nicotine (0.4 mg/kg s.c.) on locomotor activity in photocell cages have been compared in male, female, and ovariectomized hooded rats. In Experiment 1, female rats displayed higher locomotion than males (n = 12); acutely, nicotine-reduced locomotion, and this effect was slightly larger in females than males. Daily administration of nicotine for 21 days produced a similar, gradual increase in activity in both sexes. Tests then confirmed greater activity in females than males and as a function of previous chronic exposure to nicotine (n = 6); there was an activating effect of nicotine challenge but no interaction of nicotine effects with sex. In Experiment 2, ovariectomized rats were primed with 17-beta-estradiol (50 microg/kg s.c.) and progesterone (2.5 mg/kg s.c.) or vehicle only. Acute administration of nicotine reduced activity in both groups similarly (n = 12). After nicotine daily for 21 days, there was increased activity as a function of both chronic nicotine and hormonal priming, and challenge with nicotine increased activity (n = 6). The effects of these challenges with nicotine were also slightly greater, as a function of previous nicotine exposure and priming. As a whole, these experiments showed robust effects of acute and chronic nicotine administration, sex, and hormonal priming; neither sex nor gonadal hormones had marked influences on changes in locomotor activity produced by nicotine.

Discriminative stimulus properties of the nicotinic agonist cytisine

Cytisine binds with high affinity and specificity to neuronal nicotinic receptors but its physiological and behavioural effects are complex and differ from those of nicotine. The present study explores the behavioural aspects further by comparing the discriminative stimulus effects of cytisine with those of nicotine. Two groups of rats were trained to discriminate cytisine (2 mg/kg SC) or nicotine (0.2 mg/kg SC) from saline in a two-lever operant conditioning procedure with food reinforcers presented on a tandem VI FR schedule. A third group of rats was trained to discriminate cytisine (3 mg/kg SC). Rats acquired these discriminations within 50 training sessions. The stimulus effects of both cytisine and nicotine appeared within 4 min of SC injection. In generalization tests, rats trained with either cytisine or nicotine showed steep dose-response curves (generalization gradients) for their respective training drug. However, rats trained with cytisine showed full dose-related, generalization to nicotine (93%), whereas rats trained with nicotine exhibited only partial generalization to cytisine (54%). Rats trained with either cytisine or nicotine exhibited similar, partial generalization (76–77%) to (+)-amphet-amine. The nicotine antagonist mecamylamine blocked the discriminative stimulus effects of both cytisine and nicotine; it was confirmed that the block of nicotine (0.2 mg/kg) was complete, whereas the block of cytisine (2 and 3 mg/kg) was incomplete in two separate experiments. Overall, the results showed that cytisine, like nicotine, can serve as a robust discriminative stimulus but, in contrast to its relatively high affinity in binding experiments, cytisine was much less potent than nicotine in the behavioural studies. Although the stimulus effects of the two drugs were very similar, there were some subtle differences such as the asymmetrical cross-generalizations between them and possible small differences in susceptibility to antagonism by mecamylamine. These effects were interpreted either in terms of a putative partial agonist effect of cytisine, or by assuming that nicotine produces a compound stimulus. Such a stimulus would be mediated through two or more subtypes of nicotinic receptor, and cytisine would act at some, but not all, of these receptor subtypes.

Motor depression: A new role for D1 receptors?

The aims of this study were two-fold. Firstly, to characterize the behavioral properties of a potential new dopamine D1 receptor agonist, (-)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo[4,3-ab]phenanth ridine (CY 208-243), to determine its suitability as a tool for investigating D1 receptor function in vivo. Secondly, to investigate how the behavioural properties of D1 agonists are modified in the presence of D2 receptor blocking drugs. For this purpose, using mice, we employed CY 208-243 and 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393) as reference D1 agonists, and the substituted benzamides metoclopramide and sulpiride as selective D2 antagonists. CY 208-243 (0.25-10 mg/kg) caused only a modest increase in grooming in non-habituated mice, but stimulated locomotion, rearing, grooming and orofacial activities in habituated animals. These responses were inhibited by a D1 antagonist, but not by D2 antagonists, suggesting CY 208-243 behaves as a selective agonist of D1 receptors in vivo. In non-habituated mice, doses of metoclopramide and sulpiride which had little or no effect on motor behaviour by themselves, interacted synergistically with CY 208-243 (4 mg/kg) and SKF 38393 (30 mg/kg) to cause extended periods of immobility. Other species-typical behaviours were not affected in this way. For example, grooming was decreased by metoclopramide and increased by sulpiride, indicating that an increase in behavioural competition from this parameter was not the cause of the hypokinesia. To explain the apparent ability of D1 receptor stimulation to increase exploratory activity in earlier experiments and to decrease it here, it is proposed that this behaviour is regulated by D1 receptors coupled to two functionally opposite postsynaptic D2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of alcohol dependence on automatic visuo-spatial perspective taking

BACKGROUND Alcoholism is associated with cognitive deficits that affect social functioning. Previous research has shown that alcoholism is associated with deficits in conscious, deliberate social processing. However, little is known about whether alcoholism also affects rapid, spontaneous processing. We therefore investigated the extent to which alcoholism affects the ability to spontaneously adopt the viewpoint of another in a visuo-spatial perspective taking (VSPT) task. METHODS VSPT was measured in participants responding to a dot probe presented for 35ms alongside neutral faces, fearful faces and baseline stimuli (rectangles). RESULTS Non alcohol dependent participants showed the standard reaction time cost to fearful faces, but not neutral faces relative to baseline. However, Alcohol dependent (AD) participants showed a reaction time cost to both fearful and neutral faces. CONCLUSIONS AD participants are not impaired in their ability to automatically adopt the perspective of another. However, unlike non-AD participants, they show automatic perspective taking to both neutral and fearful faces.

The Dopamine D4 Receptor Gene (DRD4) is Associated with Attentional Bias in Heroin Abusers and Cigarette Smokers

The search for a genetic vulnerability gene for substance abuse has focused on dopaminergic genes, including the DRD4 receptor. In addition to clear biological mechanisms in substance abuse, many studies have found a psychologi- cal attentional bias to drug-related stimuli in substance users. This study aimed to determine whether a DRD4 gene poly- morphism is associated with such attentional biases to substance-related stimuli. Eighty heroin abusers in treatment, 80 cigarette smokers, 80 alcohol abusers in treatment and 80 non-smoking community controls undertook an emotional Stroop task to measure attentional bias to drug-related stimuli. DNA was obtained from cheek cell samples and the DRD4 VNTR polymorphism genotyped. Heroin abusers and cigarette smokers, but not controls, who carried the long variant at the DRD4 gene spent significantly longer responding to drug-related stimuli than they did to neutral stimuli when com- pared to those who did not carry the long variant at the DRD4 gene. A non-significant trend to delay was observed in al- coholics. These findings suggest that variants at the DRD4 gene influence attentional bias in substance abusers and offer further insight into the role of the DRD4 gene in drug dependence as well as individual differences in the susceptibility to attentional bias to drug-related environmental cues.

RELATIONSHIPS BETWEEN BREAST-FEEDING, CO-SLEEPING, AND SOMATIC COMPLAINTS IN EARLY CHILDHOOD

The central aim of this study was to expand a limited body of knowledge on the complex relationship between breast-feeding, co-sleeping, and somatic complaints in early childhood. An opportunity sample of 98 parents from the general population with children aged 18 to 60 months consented to participate in the study. Each parent completed a series of questionnaires measuring somatic complaints, sleep problems, co-sleeping, breast-feeding, and demographic factors. Findings indicated that co-sleeping was associated with increased somatic complaints and that breast-feeding associated with decreased somatic complaints. Co-sleeping also was found to be associated with an increase in sleep problems. Boys demonstrated significantly higher levels of sleep problems than did girls. These findings highlight the relationship between co-sleeping during early childhood, which could have implications for prevention, treatment, and intervention regarding somatic complaints and sleep problems in early childhood.