Central serotonin2C receptor: from physiology to pathology

Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has explored the pathophysiological role of one of these receptors, the 5-HT2C receptor, that has been emerged as a prominent central serotonin receptor subtype. The physiology, pharmacology and anatomical distribution of the 5-HT2C receptors in the CNS will be firstly reviewed. Finally, their potential involvement in the pathophysiology of depression, schizophrenia, Parkinson's disease and drug abuse will be also discussed.     

Univentricular heart: An angiographic study

Axial angiograms of 54 patients with a univentricular heart were reviewed to determine the anatomic details demonstrated by this technique. The main ventricular chamber was of left ventricular morphology in 36, right ventricular morphology in 13 and indeterminate in 5 patients. Forty-three patients had a rudimentary ventricular chamber that was supporting a great artery in 35 patients. Eighteen patients had separate atrioventricular (A-V) valves. In four of them, one A-V valve was overriding the trabecular septum, but predominantly committed to the main ventricular chamber. Eleven patients had a single right and 13 a single left A-V valve; a common A-V valve was present in 12.The techniques used provided good demonstration of the morphology of the ventricular mass, particularly the position and orientation of a septum when present. They also delineated the morphology of the A-V valve or valves and their precise ventricular connection. Ventriculoarterial connections and relations were readily determined. It is concluded that these methods are superior to isolated frontal and lateral views and provide thorough demonstration of the intracardiac anatomy of patients with a univentricular heart.     

The neurobiological bases for the pharmacotherapy of nicotine addiction

Nicotine, the major psychoactive agent present in tobacco, acts as a potent addictive drug both in humans and laboratory animals, whose locomotor activity is also stimulated. A large body of evidence indicates that the locomotor activation and the reinforcing effects of nicotine may be related to its stimulatory effects on the mesolimbic dopaminergic function. Thus, it is now well established that nicotine can increase in vivo DA outflow in the nucleus accumbens and the corpus striatum. The stimulatory effect of nicotine on DA release most probably results from its ability to excite the neuronal firing rate and to increase the bursting activity of DA neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), and from its stimulatory action on DA terminals in the corpus striatum and the nucleus accumbens. The neurochemical data are consistent with neuroanatomical findings showing the presence of nicotinic acetylcholine receptors (nAChRs) in the SNc, the VTA, and in projection areas of the central dopaminergic system such as the corpus striatum and the nucleus accumbens. Several lines of evidence indicate that the reinforcing properties of drugs of abuse, including nicotine, can be affected by a number of transmitter systems which may act by modulating central dopaminergic function. In this paper, the neurobiological mechanisms underlying nicotine addiction will be reviewed, and the possible strategies for new pharmacological treatments of nicotine dependence will be examined.     

DNA damage in brain cells and behavioral deficits in mice after treatment with high doses of amantadine

Amantadine (AMA) is an uncompetitive antagonist of the N‐methyl‐d ‐aspartate receptor, with clinical application, acting on treatment of influenza A virus and Parkinson's disease. It has been proposed that AMA can indirectly modulate dopaminergic transmission. In high doses, the central nervous system is its primary site of toxicity. To examine deleterious effects on CNS induced by AMA, this study evaluated possible neurobehavioral alterations induced by AMA such as stereotyped behavior, the effects on locomotion and memory and its possible genotoxic/mutagenic activities. Adult male CF‐1 mice were treated with a systemic injection of AMA (15, 30 or 60 mg kg^?1) 20 min before behavioral tasks on open field and inhibitory avoidance. Higher AMA doses increased the latency to step‐down inhibitory avoidance test in the training session in the inhibitory avoidance task. At 60 mg kg^?1 AMA induced impairing effects on locomotion and exploration and hence impaired habituation to a novel environment. Stereotyped behavior after each administration in a 3‐day trial was observed, suggesting effects on dopaminergic system. Amantadine was not able to induce chromosomal mutagenesis or toxicity on bone marrow, as evaluated by the micronucleus assay. At the lowest dose tested, AMA did not induce DNA damage and it was unable to impair memory, locomotion, exploration or motivation in mice. However, higher AMA doses increased DNA damage in brain tissue, produced locomotor disturbances severe enough to preclude testing for learning and memory effects, and induced stereotypy, suggesting neurotoxicity.     

Influence of Substance Use Disorders on 2-Year HIV Care Retention in the United States

Substance use disorders (SUDs) are thought to predict care discontinuity, though magnitude and substance-specific variance of effects are unclear. This report of analytic work undertaken with a multi-regional American cohort of 9153 care enrollees addresses these gaps. Care retention was computed from 24-month post-linkage clinic visit documentation, with SUD cases identified from patient-report screening instruments. Two generalized estimating equations tested binary and hierarchial SUD predictors of retention, and potential effect modification by patient age-group, sex, and care site. Findings demonstrate: (1) detrimental SUD effect, equivalent to a nine percentage-point decrease in retention, with independent effects of age-group and care site; (2) substance-specific effect of marijuana UD associated with lower retention; and (3) age-modification of each effect on care discontinuity, with SUDs serving as a risk factor among 18–29 year-olds and protective factor among 60+ year-olds. Collective findings document patient attributes as influences that place particular subgroups at-risk to discontinue care.