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One of the leading drug addiction theories states that habits and the underlying neural process of a ventral to dorsal striatal shift are the building blocks of compulsive drug‐seeking behaviour and that compulsion is the maladaptive persistence of responding despite adverse consequences. Here we discuss that compulsive behaviour as defined primarily from the perspective of animal experimentation falls short of the clinical phenomena and their neurobiological correlates. Thus for the human condition, the concept of compulsive habits should be critically addressed and potentially revised. [ABSTRACT FROM AUTHOR]

The purpose of this study was to prove the direct correlation of a successions of gravel‐clay beds recovered in borehole with the melt‐water pulses associated with the sea‐level oscillations indicated in the δ18O record in the time‐span preceding the 100‐kyr glacial cycles. Aimed at this scope, we provide combined 40Ar/39Ar and paleomagnetic constraints to a set of seven aggradational successions recovered from a 120 m deep borehole drilled in the buried Paleo‐Tiber delta in Rome (central Italy). The geochronologic constraints enable the correlation of each aggradational succession, characterized by a sudden transition from coarse gravel at the base to sandy clay sediments, with periods of sea‐level rise indicated by the δ18O curve encompassing MIS 37 through MIS 19, from 1250 to 780 ka. This stratigraphy, provides a unique and unprecedented well‐dated evidence of glacial/deglacial events, matching the global benthic δ18O stack during this time frame. Furthermore, this study validates the hypothesis that gravel deposition in the catchment basin and the delta of the main rivers in central Italy is triggered by the melting of glaciers in the Apennines Mountain range. It demonstrates the significant potential of these deglaciation proxies to be used worldwide to unravel the chronology of glacio‐eustatic events. Plain Language Summary: In this study, we used a combination of dating techniques and paleomagnetic data to examine a series of sediment layers found in a buried ancient river delta in Rome, Italy. These sediment layers were collected from a 120 m deep borehole. By analyzing the age of these sediment layers, we were able to link them to a period in the past when sea level was rising. This sea‐level rise occurred between 1250 and 780 ka, covering a range of time from MIS 37 to MIS 19. These sediment layers show a distinct change from coarse gravel to sandy clay, which provides valuable information about glacial and deglacial events. These findings support the idea that the deposition of gravel in river catchment areas and deltas in central Italy is linked to the melting of glaciers in the Apennines Mountain range. This research not only validates this hypothesis but also highlights the potential for using similar techniques globally to better understand the timing of glacio‐eustatic events. Key Points: We provide 40Ar/39Ar and paleomagnetic constraints to seven aggradational successions recovered from a 120 m deep borehole in RomeEach aggradational succession is correlated with a period of sea‐level rise encompassing MIS 37 through MIS 19, 1250 to 780 kaThis study shows that gravel deposition in the catchment basin of the main rivers in central Italy is a direct proxy of deglacial events [ABSTRACT FROM AUTHOR]

The documentation and understanding of variations in the Earth's magnetic field through time is fundamental for several disciplines, but current geomagnetic models rely on datasets heavily biased toward the mid‐ and high northern latitudes. The African continent and surrounding islands and oceans are particularly underrepresented. Here, we present a new record of paleo‐secular variation (PSV) of the inclinations over the last 23 ka from Lake Chala, situated at 3°S near Mt Kilimanjaro in eastern equatorial Africa. This groundwater‐fed crater lake is characterized by a high sedimentation rate (ca. 1 cm/10 years) and a particularly well‐constrained age model based on 210Pb and 14C dating. The magnetic mineralogy of the sediments is tested with rock magnetic analyses. The Lake Chala inclination record shows four highs and lows over 20 ka and compares well with that of Lake Malawi (10°S) between 20 and 16.2 ka, and from 9.8 to 2.6 ka. This record is linked to PSV records at Lakes Victoria and Malawi using a sequence slotting technique to generate a composite PSV model for east Africa. Analyzed at best‐possible resolutions up to 200 years, the Lake Chala PSV record not only represents an important contribution to improve our understanding of local and global features of the Earth's magnetic field. It also expands the utility of paleomagnetism as a key tool for dating and correlation both for archeological sites throughout East Africa and the many volcanoes, active or dormant, of the East African Rift System. Plain Language Summary: The understanding of the behavior of the Earth's Magnetic field in the geological past is based on an even spatial and temporal distribution of data collections. Nonetheless, data from large areas, such as from the African continent, remain sparse. In this study, we present new data from Lake Chala in equatorial East Africa, near Mount Kilimanjaro. The new inclination data are measured in lacustrine sediments covering the last 23 ka. We combine the data from Lake Chala with other data from Lake Victoria and Lake Malawi to produce a composite record for east African Lakes, using sequence slotting which improves the coherence between the records, whilst still constrained by the sediment age models. The composite record, centered on Lake Chala, improves our understanding of how the Earth's magnetic field changed in the recent past and can serve as an independent tool for dating nearby archeological sites as well as volcanic deposits from the African Rift emplaced in the last 23 ka. Key Points: Lake Chala contains an exceptionally well‐dated paleosecular variation record for east AfricaSequence slotting is used to refine a match to other secular variation records from east African lakesA composite paleosecular variation for equatorial east Africa is produced utilizing the combined set of control dates and magnetic records [ABSTRACT FROM AUTHOR]

Aim: Children have largely been unaffected by severe COVID‐19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID‐19 and healthy controls. Methods: A retrospective nested cohort study assessed the incidence rate of new‐onset conditions after COVID‐19 in children aged 0–14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. Results: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new‐onset conditions after COVID‐19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1–3.0) and neurological problems (aHR 2.4, 95% CI 1.4–4.1). Conclusion: Exposed children had a 78% higher risk of developing new conditions of interest after COVID‐19 than unexposed children. [ABSTRACT FROM AUTHOR]

The NE‐dipping Anghiari normal fault, bounding to the west the Sansepolcro basin in the Upper Tiber Valley (northern Apennines), is thought to be a synthetic splay of the Altotiberina low‐angle normal fault (LANF), an active ENE‐dipping extensional detachment whose seismogenic behavior is debated. In order to assess the Anghiari fault capability to break the surface during strong earthquakes and be the source of historical earthquakes, we acquired high resolution topographic data, performed field survey and geophysical investigations (Seismic reflection, Ground Penetrating Radar, Electrical Resistivity Tomography) and dug three paleoseismological trenches across different fault sections of the Anghiari fault. The acquired data reveal for the first time the Late Pleistocene to historical activity of the Anghiari fault, constraining the age of seven paleo‐earthquakes over the last 25 ka, the youngest of which is comparable with one of the poorly constrained historical earthquakes of the Sansepolcro basin. The yielded slip rate is >0.2 mm/yr averaged over the last 25 ka and the recurrence interval is about 2,500–3,200 years. An analysis of the anisotropy of the magnetic susceptibility performed in one of the paleoseismological trenches revealed an extensional stress field, continuously acting during the sedimentation of the entire trenched stratigraphy. Our results confirm the ability of the Anghiari fault to generate surface faulting earthquakes. In addition, if the Anghiari fault does sole at depth into the Altotiberina low‐angle normal fault, this LANF could also be seismogenic and generate M > 6. Plain Language Summary: We analyzed the capability of the Anghiari fault (Upper Tiber Valley, Northern Apennines of Italy) to reach and break the topographic surface during a strong earthquake. This fault may links to the Altotiberina low‐angle normal fault (ATF), a detachment fault accompanied by a system of synthetic splays whose seismogenic behavior is still debated because of a lack of seismological and paleoseismological data. Thanks to geological, morphological, and geophysical analyses, four sites have been selected for paleoseismological investigation. The paleoseismological data revealed the seismic history of the Anghiari fault, assessing its capability to recurrently break the surface during strong earthquakes. In addition, an analysis of the anisotropy of the magnetic susceptibility performed in one of the paleoseismological trenches indicates that the stress field has been extensional, acting continuously during the sedimentation of the entire trenched stratigraphy. Our results suggest that the AF is capable to break the surface during strong earthquakes. This has potential implications for the seismogenic behavior of the ATF low‐angle normal fault, as the strong earthquakes (M > 6) may nucleate on the low‐angle fault plane if the AF is soling at depth into that detachment. Key Points: Revealed the Late Pleistocene—Holocene slip history of the Anghiari fault, considered a synthetic splay of a low‐angle normal faultThe capability of the Anghiari fault to rupture the surface during M > 6 earthquakes has been ascertainedThe results have potential implications for the activity and seismogenic behavior of a continental low‐angle normal faults [ABSTRACT FROM AUTHOR]

Background and Purpose: Spice/K2 herbal mixtures, containing synthetic cannabinoids such as JWH‐018, have been marketed as marijuana surrogates since 2004. JWH‐018 has cannabinoid CB1 receptor‐dependent reinforcing properties and acutely increases dopaminergic transmission selectively in the NAc shell. Here, we tested the hypothesis that repeated administration of JWH‐018 (i) modulates behaviour, (ii) affects dopaminergic transmission and its responsiveness to motivational stimuli, and (iii) is associated with a neuroinflammatory phenotype. Experimental Approach Rats were administered with JWH‐018 once a day for 14 consecutive days. We then performed behavioural, electrophysiological, and neurochemical evaluation at multiple time points after drug discontinuation. Key Results: Repeated JWH‐018 exposure (i) induced anxious and aversive behaviours, transitory attentional deficits, and withdrawal signs; (ii) decreased spontaneous activity and number of dopamine neurons in the VTA; and (iii) reduced stimulation of dopaminergic transmission in the NAc shell while potentiating that in the NAc core, in response to acute JWH‐018 challenge. Moreover, (iv) we observed a decreased dopamine sensitivity in the NAc shell and core, but not in the mPFC, to a first chocolate exposure; conversely, after a second exposure, dialysate dopamine fully increased in the NAc shell and core but not in the mPFC. Finally, selected dopamine brain areas showed (v) astrogliosis (mPFC, NAc shell and core, VTA), microgliosis (NAc shell and core), and downregulation of CB1 receptors (mPFC, NAc shell and core). Conclusion and Implications: Repeated exposure to JWH‐018 may provide a useful model to clarify the detrimental effects of recurring use of Spice/K2 drugs. [ABSTRACT FROM AUTHOR]

Constraining the long‐term variability and average of the Earth's magnetic field strength is fundamental to understanding the characteristics and behavior of the geomagnetic field. Questions remain about the strength of the average field, and the relationship between strength and reversal frequency, due to the dispersion of data from key time intervals. Here, we focus on the Cretaceous Normal Superchron (CNS; 121‐84 Ma), during which there were no reversals. We present new intensity results from 41 submarine basaltic glass (SBG) sites collected on the Nicoya Peninsula and Murcièlago Islands, Costa Rica. New and revised 40Ar/39Ar and biostratigraphic age constraints from previous studies indicate ages from 141 to 65 Ma. One site with an age of 135.1 ± 1.5 Ma (2σ) gave a reliable intensity result of 34 ± 8 µT (equivalent to a virtual axial dipole moment, VADM, value of 88 ± 20 ZAm2), three sites from 121 to 112 Ma, spanning the onset of the CNS, vary from 21 ± 1 to 34 ± 4 µT (53 ± 3 to 87 ± 10 ZAm2). These results from the CNS are all higher than the long‐term average of ∼42 ZAm2 and data from Suhongtu, Mongolia (46–53 ZAm2) and are similar to the Troodos Ophiolite, Cyprus (81 ZAm2, reinterpreted in this study). Together with the reinterpreted data, the new Costa Rica results suggest that the strength of the geomagnetic field was approximately the same both before and after the onset of the CNS. Therefore, the data do not support a strict correlation between polarity interval length and the strength of the magnetic field. Plain Language Summary: Understanding the Earth's magnetic field behavior in the past is important to validate geodynamo simulations. However, because of the paucity of available data, it is poorly understood. In particular, it has been argued that the strength of the Earth's magnetic field, or paleointensity, was correlated with the stability of the field, where a strong field was less prone to magnetic reversals than a weak field. Hence, we have investigated the anomalously long period of stability, the Cretaceous Normal Superchron (CNS) during which no magnetic reversals occurred. Our new data from Costa Rican basaltic glasses, together with reinterpreted data from Inner Mongolia and the Troodos Ophiolite in Cyprus, suggest that the magnetic field during the CNS was similar to the present‐day field and these high values are nearly twice the long‐term average value for the last 200 Ma. However, high field values were also detected in the period prior to the onset of the CNS, hence our data do not support a strict correlation between strength and stability of the Earth's magnetic field. Key Points: The Cretaceous Normal Superchron (CNS) is key to understanding geomagnetic field behaviorWe present new paleointensity data from Costa Rica over an age range of 135–112 Ma, spanning the onset of the CNSWe find that field strength was high both prior and during the early CNS, which does not support a correlation between field strength and stability [ABSTRACT FROM AUTHOR]

The Chiloé fore‐arc sliver is an approximately N‐S elongated crust block detached from South America along the dextral intra‐arc Liquiñe‐Ofqui fault zone (LOFZ). The sliver is internally dissected by active NW‐SE sinistral faults whose relations with the LOFZ are speculative, also due to widespread fluvioglacial and volcanic blanket hiding the substratum. We focus on the northern LOFZ end and on the Biobio fault, supposedly the northernmost of the sinistral fault set, reporting on the results from field investigation and paleomagnetism of 48 (mostly Oligo‐Miocene) volcanic sites. We find that the Biobio fault is an old inherited crust discontinuity that did not yield significant block rotation and deformation during the Cenozoic, thus testifying the end of sinistral shear at about 38°S. At the same latitudes, a northward transition from pure strike‐slip to transpressive LOFZ deformation occurs. Intense tectonic deformation and >90° clockwise rotations characterize the main LOFZ strand. Conversely, a supposedly western LOFZ strand displays counterclockwise rotations, similar to the pattern previously documented in the forearc; thus, it does not represent a LOFZ segment. LOFZ and sinistral fault kinematics must be related, and we suggest that crust pushed northward west of the LOFZ escapes laterally toward the trench along the sinistral faults. We also speculate that the northward increasing age of the subducting Nazca plate implies a concomitant decrease of heat transfer on the upper plate, thus an increasing crust rigidity that eventually inhibits strain partitioning and sliver decoupling from 38°S. Key Points: The Chiloé sliver ends at 38°S where the Liquiñe‐Ofqui fault becomes transpressive, and it crosses the inactive Biobio fault traceCrust pushed northward by dextral shear along the Liquiñe‐Ofqui fault escapes westward reactivating NW‐SE faults with sinistral offsetThe transition from a detached fore‐arc sliver to Andean‐type chain is controlled by the heat budget in the lower‐upper plates system [ABSTRACT FROM AUTHOR]

Loren (Larry) H. Parsons passed away at the age of 51. In spite of his premature departure, Larry much contributed to the drug abuse field. Since his graduate studies for the Ph.D. in Chemistry in J.B. Justice lab, microdialysis is the tread that links Larry's research topics, namely, the role of dopamine (DA), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate and endocannabinoids (eCBs) in drug reinforcement and dependence. Larry was the first to show that abstinence from chronic cocaine reduces extracellular DA in the NAc, consistent with the so called 'dopamine depletion hypothesis' of cocaine addiction. Another Larry's major contributions are the studies on 5-HT and 5-HT receptors' role in cocaine stimulant actions, which resulted in the identification of 5-HT1B receptors as a critical substrate of cocaine reinforcement. By applying mass spectrometry to eCBs analysis in brain dialysates, Larry's lab showed that ethanol, heroin, nicotine and cocaine differentially affect anandamide and 2-arachidonoylglicerol overflow in the NAc shell, a critical site of drugs of abuse DA stimulant actions. Larry also applied microdialysis to study GABA and glutamate's role in ethanol dependence and heroin reinforcement, providing in vivo evidence for a sensitization of corticotropin-releasing factor-dependent release of GABA in the central amygdala in withdrawal from chronic ethanol and for a reduction of GABA transmission in the ventral pallidum in heroin but not cocaine intravenous self-administration. Larry showed the wide possibilities of microdialysis as a general purpose methodology for monitoring neurotransmitters and neuromodulators in the brain extracellular compartment. From this viewpoint, he stands as the best advocate for microdialysis. [ABSTRACT FROM AUTHOR]

A recent hypothesis has suggested that Earth's inner core nucleated during the Mesoproterozoic, as evidenced by a rapid increase in the paleointensity (ancient geomagnetic field intensity) record; however, paleointensity data during the Paleoproterozoic and Mesoproterozoic period are limited. To address this problem, we have determined paleointensity from samples from three Paleoproterozoic Avanavero mafic sills (Amazonian Craton, Brazil): Cotingo, 1,782 Ma, Puiuà, 1,788 Ma, and Pedra Preta, 1,795 Ma. We adopted a multiprotocol approach for paleointensity estimates combining Thellier-type IZZI and LTD-IZZI methods, and the nonheating Preisach protocol. We obtained an average VDM value of 1.3 ± 0.7 × 1022Am2 (Cotingo) of 2.0 ± 0.4 × 1022Am2 (Puiuà) and 6 ± 4 × 1022Am2 (Pedra Preta); it is argued that the Cotingo estimate is the most robust. Our results are the first data from the upper Paleoproterozoic for South America and are comparable to data available from other regions and similar periods. The new data do not invalidate the hypothesis of that Earth's inner core nucleated during the Mesoproterozoic. [ABSTRACT FROM AUTHOR]

Aims: Despite advances in the management of patients with acute coronary syndrome (ACS), cardiogenic shock (CS) remains the leading cause of death in these patients. We describe the evolution of clinical characteristics, in-hospital management, and outcome of patients with CS complicating ACS.Methods and Results: We analysed data from five Italian nationwide prospective registries, conducted between 2001 and 2014, including consecutive patients with ACS. Out of 28 217 ACS patients enrolled, 1209 (4.3%) had CS: 526 (44%) at the time of admission and 683 (56%) later on during hospitalization. Over the years, a reduction in the incidence of CS was observed, even though this was not statistically significant (P for trend = 0.17). The proportions of CS patients with a history of heart failure declined, whereas the proportion of those with hypertension, renal dysfunction, previous PCI, and AF significantly increased. The use of PCI considerably increased from 2001 to 2014 [19% to 60%; percentage change 41, 95% confidence interval (CI) 29-51]. In-hospital mortality of CS patients decreased from 68% (95% CI 59-76) in 2001 to 38% (95% CI 29-47) in 2014 (percentage change -30, 95% CI -41 to -18). Compared with 2001, the risk of death was significantly lower in all of the registries, with reductions in adjusted mortality between 45% and 66%.Conclusions: Over the last 14 years, substantial changes occurred in the clinical characteristics and management of patients with CS complicating ACS, with a greater use of PCI and a significant reduction in adjusted mortality rate. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the impact of educational status on global cardiovascular risk in a southern Italian urban population. The study population consisted of 488 consecutive outpatients aged 18 years and older. Educational status was categorized according to the number of years of formal education as follows: (1) low education group (<10 years) and (2) medium-high education group (10-15 years). In both groups, cardiometabolic comorbidities (obesity, visceral obesity, diabetes, dyslipidemia, metabolic syndrome, microalbuminuria, left ventricular hypertrophy) and global cardiovascular risk, according to international guidelines, were analyzed. Left ventricular mass index and ejection fraction by echocardiography and E/A ratio, by pulsed-wave Doppler, were calculated. The low education group was characterized by a significantly higher prevalence of patients with visceral obesity ( P=.021), hypertension ( P=.010), metabolic syndrome ( P=.000), and microalbuminuria ( P=.000) and greater global cardiovascular risk ( P=.000). Significantly increased levels of microalbuminuria ( P=.000) and significantly decreased values of E/A ratio ( P=.000) were also detected in the low education group. Global cardiovascular risk correlated directly with waist-to-hip ratio ( P=.010), microalbuminuria ( P=.015), and the metabolic syndrome ( P>.012) and inversely with educational status ( P=.000). Education was independently ( P=.000) associated with global cardiovascular risk. These data indicate a strong association between low education and cardiometabolic comorbidities suitable to influence the evolution of chronic degenerative diseases. Preventive strategies need to be more efficient and more effective in this patient population. [ABSTRACT FROM AUTHOR]

This study investigated by microdialysis the role of response contingency and food-associated cues in the responsiveness of dopamine transmission in the nucleus accumbens shell and core to sucrose feeding. In naive rats, single-trial non-contingent presentation and feeding of sucrose pellets increased dialysate shell dopamine and induced full habituation of dopamine responsiveness to sucrose feeding 24 and 48 h later. In rats trained to respond for sucrose pellets on a fixed ratio 1 (FR1) schedule, dialysate dopamine increased in the shell but not in the core during active responding as well as under extinction in the presence of sucrose cues. In rats yoked to the operant rats, the presentation of sucrose cues also increased dialysate dopamine selectively in the shell. In contrast, non-contingent sucrose presentation and feeding in FR1-trained and in yoked rats increased dialysate dopamine to a similar extent in the shell and core. It is concluded that, whereas non-contingent sucrose feeding activated dopamine transmission in the shell and core, response-contingent feeding activated, without habituation, dopamine transmission selectively in the shell as a result of the action of sucrose conditioned cues. These observations are consistent with a critical role of conditioned cues acquired during training and differential activation of shell vs. core dopamine for response-contingent sucrose feeding. [ABSTRACT FROM AUTHOR]

Adolescent Cannabis exposure has been hypothesized to act as a gateway to opiate abuse. In order to investigate the role of genetic background in cannabinoid-opiate interactions, we studied the effect of Δ9-tetrahydrocannabinol ( THC) exposure of adolescent Lewis and Fischer 344 rats on the responsiveness of accumbens shell and core dopamine ( DA), as monitored by microdialysis, to THC and heroin at adulthood. Heroin reward and reinstatement by heroin priming were studied by conditioned place preference ( CPP) and cognitive and emotional functions by object recognition, Y maze and elevated plus maze paradigms. THC stimulated shell DA in Lewis but not in Fischer 344 rats. Adolescent THC exposure potentiated DA stimulant effects of heroin in the shell and core of Lewis and only in the core of Fischer 344 rats. Control Lewis rats developed stronger CPP to heroin and resistance to extinction compared with Fischer 344 strain. In Lewis rats, THC exposure did not affect heroin CPP but potentiated the effect of heroin priming. In Fischer 344 rats, THC exposure increased heroin CPP and made it resistant to extinction. Lewis rats showed seeking reactions during extinction and hedonic reactions in response to heroin priming. Moreover, adolescent THC exposure affected emotional function only in Lewis rats. These observations suggest that long-term effects of Cannabis exposure on heroin addictive liability and emotionality are dependent on individual genetic background. [ABSTRACT FROM AUTHOR]

The Liquiñe-Ofqui fault zone (LOFZ) is a major ~1000 km long dextral shear zone of southern Chile, likely related to strain partitioning of Nazca Plate oblique convergence with South America. To understand block rotation pattern along the LOFZ, we paleomagnetically sampled 55 sites (553 samples) between 38°S and 41°S. We gathered Oligocene to Pleistocene volcanics and Miocene granites at a maximum distance of 20 km from the LOFZ, and at both sides of it. Rotations with respect to South America, evaluated for 36 successful sites, show that crust around the LOFZ is fragmented in small blocks, ~1 to 10 km in size. While some blocks (at both fault edges) undergo very large 150°-170° rotations, others do not rotate, even adjacent to fault walls. We infer that rotations affected equidimensional blocks, while elongated crust slivers were translated subparallel to the LOFZ, without rotating. Rotation pattern across the LOFZ is markedly asymmetric. East of the fault and adjacent to it, rotations are up to 150°-170° clockwise, and fade out ~10 km east of fault. These data support a quasi-continuous crust kinematics, characterized by small rigid blocks drag by the underlying ductile crust flow, and imply 120 km of total fault offset. Conversely, crust west of the LOFZ is cut by seismically active NW-SE sinistral antithetic faults, and yields counterclockwise rotations up to 170° at 8-10 km from LOFZ, besides the unrotated blocks. Further data from the Chile fore arc are needed to understand block rotation kinematics and plate dynamics west of the LOFZ. [ABSTRACT FROM AUTHOR]

Taste stimuli increase extracellular dopamine ( DA) in the nucleus accumbens ( NAc) and in the medial prefrontal cortex (m PFC). This effect shows single-trial habituation in NAc shell but not in core or in m PFC. Morphine sensitization abolishes habituation of DA responsiveness in NAc shell but induces it in m PFC. These observations support the hypothesis of an inhibitory influence of m PFC DA on NAc DA. To test this hypothesis, we used in vivo microdialysis to investigate the effect of m PFC 6-hydroxy-dopamine (6- OHDA) lesions on the NAc DA responsiveness to taste stimuli. 6- OHDA was infused bilaterally in the m PFC of rats implanted with guide cannulae. After 1 week, rats were implanted with an intraoral catheter, microdialysis probes were inserted into the guide cannulae, and dialysate DA was monitored in NAc shell/core after intraoral chocolate. 6- OHDA infusion reduced tissue DA in the m PFC by 75%. Tyrosine hydroxylase immunohistochemistry showed that lesions were confined to the m PFC. m PFC 6- OHDA lesion did not affect the NAc shell DA responsiveness to chocolate in naive rats but abolished habituation in rats pre-exposed to the taste. In the NAc core, mPFC lesion potentiated, delayed and prolonged the stimulatory DA response to taste but failed to affect DA in pre-exposed rats. Behavioural taste reactions and motor activity were not affected. The results indicate a top-down control of NAc DA by mPFC and a reciprocal relationship between DA transmission in these two areas. Moreover, habituation of DA responsiveness in the NAc shell is dependent upon an intact DA input to the mPFC. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) represents a combination of cardiometabolic risk factors, including visceral obesity, glucose intolerance or type 2 diabetes, elevated triglycerides, reduced HDL cholesterol, and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the "epidemic" obesity, with a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. At present, there is a growing interest on the role of visceral fat accumulation in the occurrence ofMetS. In this review, the effects of adipocytokines and other proinflammatory factors produced by fat accumulation on the occurrence of theMetS have been also emphasized. Accordingly, the "hypoadiponectinemia" has been proposed as the most interesting new hypothesis to explain the pathophysiology of MetS. [ABSTRACT FROM AUTHOR]

The aim of this research was to study the role of dopamine D1 receptors in caffeine elicited ERK phosphorylation in the prefrontal and other cortical (cingulate and motor) and subcortical (shell and core of the nucleus accumbens) regions. To this end, caffeine (3 and 10 mg/kg) was administered before phosphoERK immunohistochemistry. Caffeine dose-dependently increased the number of phosphoERK-positive neurons in the prefrontal and cingulate cortices but not in the secondary motor cortex and in the nucleus accumbens shell and core. The dopamine D1 receptor antagonist, SCH 39166 (50 μg/kg), fully prevented phosphoERK activation by caffeine (10 mg/kg) in the superficial and deep layers of the prefrontal cortex but failed to prevent it in the cingulate cortex. Given that phosphoERK can be regarded as a postsynaptic marker of neuronal activation, the present results indicate that psychotropic properties of caffeine may result from the activation of prefrontal, via dopamine D1 receptors, and cingulate cortices. Failure of caffeine to activate ERK in the nucleus accumbens further supports, indirectly, the observation that caffeine fails to activate dopamine transmission in this structure and is consistent with the tenet that caffeine lacks of true addictive properties. Synapse 64:341-349, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The distinction between malignant and benign thyroid oncocytic cell tumors (OCTs) before and during surgery still represents a diagnostic challenge. We focused on the search for specific factors that predict malignancy and influence the prognosis of OCTs, and for their most appropriate management. From January 1998 to May 2007, 57 patients underwent thyroidectomy in our surgical department because of OCT. A cross-sectional study of 28 patients with carcinoma and 29 patients with adenoma was performed: demographic data, tumor characteristics, diagnostic results, patient management, postoperative, and follow-up results were evaluated. The prevalence of malignancy was 49.1%. The mean tumor size was significantly greater for carcinomas than for adenomas (3.0 cm vs. 1.8 cm; p = 0.003). Threshold sizes of more than 3.0 cm and 4.0 cm were significant for predicting malignancy ( p = 0.020 and p = 0.010, respectively). Tumor multifocality, microfollicular features, and severe cytological atypia also were significantly related to malignancy ( p = 0.012 and p = 0.025, respectively). Recurrent OCT was observed in three patients with carcinoma. One patient with distant metastases died from the disease. Older age, tumor size, thyroid capsular invasion, higher TNM stage, and AMES high risk were factors significantly related to tumor recurrence. Multivariate analysis showed that larger tumor size was the only factor predictive of malignancy and influencing recurrence. All OCTs should be referred to surgery because of the high prevalence of malignancy. In the case of OCTs with larger tumor size and microfollicular features with severe cytological atypia, total thyroidectomy is strongly recommended as initial treatment also in relation with the more likely aggressive biological behavior of greater tumors. [ABSTRACT FROM AUTHOR]

The distribution of the T29C TGFβ1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH) and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (P < .05) higher in hypertensives with LVH than hypertensives without LVH TC and CC LVH hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (P < .05 TC and CC versus TT), by increased levels of TGFβ1, procollagen type III, urinary albumin excretion, LVM, LVM/h2.7, and lower values of left ventricular ejection fraction (P < .05 TC and CC versus TT). Our data suggest that T29C TGFβ1 gene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension. [ABSTRACT FROM AUTHOR]

Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Δ9-tetrahydrocannabinol (Δ9-THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Δ9-THC and morphine in the NAc shell and core. Different groups of male Sprague–Dawley rats were administered twice daily for 3 days with increasing doses of Δ9-THC (2, 4, and 8 mg/kg i.p.), morphine (10, 20, and 40 mg/kg s.c.), and vehicle. After 14–20 days from the last injection, the animals were implanted with two microdialysis probes, one aimed at the NAc shell and the other at the core. The following day animals pre-treated with Δ9-THC and vehicle controls were challenged with 150 μg/kg i.v. of Δ9-THC or 0.5 mg/kg i.v. of morphine. Animals pre-treated with morphine and their vehicle controls were administered with 150 μg/kg i.v. of Δ9-THC. Rats pre-exposed to Δ9-THC showed behavioral sensitization associated with a reduced stimulation of DA transmission in the NAc shell and an increased stimulation in the NAc core in response to Δ9-THC challenge. Pre-exposure to Δ9-THC induced behavioral sensitization to morphine also, but only a reduced stimulation of DA transmission in the NAc shell was observed. Animals pre-treated with morphine showed behavioral sensitization and differential changes of DA in the NAc shell and core in response to Δ9-THC challenge with a decreased response in the shell and an increased response in the core. The results show that Δ9-THC-induced behavioral sensitization is associated with changes in the responsiveness of DA transmission in the NAc subdivisions that are similar to those observed in the sensitization induced by other drugs of abuse. [ABSTRACT FROM AUTHOR]

Repeated administration of addictive drugs and prolonged exposure to stressful stimuli induce sensitization to their behavioural stimulant properties. In this study, male Sprague–Dawley rats were repeatedly exposed to morphine [twice a day for 3 days at increasing doses, 10, 20, 40 mg/kg subcutaneously (s.c)], amphetamine (1 mg/kg s.c., once a day for 10 days), nicotine (0.4 mg/kg s.c., once a day for 5 days) and stress (food restriction for 7 days). After an interval of 3–30 days, depending on the pretreatment, rats were challenged with vehicle, with the same drug received as pretreatment (5 mg/kg of morphine, 0.5 mg/kg of amphetamine or 0.4 mg/kg of nicotine, respectively) or, in the case of food-restricted rats, with 0.5 mg/kg of amphetamine. Thereafter, changes in the expression of glutamic acid decarboxylase (GAD)67 mRNA were estimated by in situ hybridization in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), dorsolateral striatum (dLStr), nucleus accumbens shell (AcS) and core (AcC). All sensitizing pretreatments increased GAD67 mRNA in the CeA. Drug challenge did not further affect GAD67 mRNA in the CeA of saline, drug and stress pre-exposed rats. As to the other areas, no differences were observed in drug pre-exposed compared with saline pre-exposed and fed ad libitum rats, except for amphetamine. Amphetamine pre-exposure decreased GAD67 mRNA levels in the dLStr and the AcC and AcS, and this effect was reversed by amphetamine challenge. The results show that different drugs and stress models of behavioural sensitization have in common an increase of GA67 in the CeA but not in the BLA, and suggest the changes of GAD67 in the CeA are a substrate of the sensitized response to drug challenge. [ABSTRACT FROM AUTHOR]

The use of inbred rat strains provides a tool to investigate the role of genetic factors in drug abuse. Two such strains are Lewis and Fischer 344 rats. Although several biochemical and hormonal differences have been observed between Lewis and Fischer 344 strains, a systematic comparison of the effect of different drugs of abuse on dopamine (DA) transmission in the shell and core of the nucleus accumbens of these strains is lacking. We therefore investigated, by means of dual probe microdialysis, the effect of different doses of morphine (1.0, 2.5, and 5.0 mg/kg), amphetamine (0.25, 0.5, and 1.0 mg/kg) and cocaine (5, 10, and 20 mg/kg) on DA transmission in the shell and in the core of nucleus accumbens. Behavior was monitored during microdialysis. In general, Lewis rats showed greater DA responsiveness in the NAc core compared to F344 rats except after 2.5 mg/kg of morphine and 20 mg/kg of cocaine. In the NAc shell, different effects were obtained depending on drug and dose: after 1.0 mg/kg of morphine no strain differences were observed, at 2.5 and 5.0 mg/kg Lewis rats showed greater increase in DA in the NAc shell. Following amphetamine and cocaine challenge, Lewis rats showed greater DA increase in the shell after 0.25 mg/kg of amphetamine and 20 mg/kg of cocaine. Behavioral activation was greater in Lewis rats in response to the lowest dose of morphine (1.0 mg/kg), to the highest dose of amphetamine (1.0 mg/kg) and to all doses of cocaine. These differences might be the basis for the different behavioral responses of these strains to drugs of abuse. [ABSTRACT FROM AUTHOR]

It has been reported that caffeine (1.5–30 mg/kg i.p.) as well as specific A1 (DPCPX, 8-cyclopentyl-1,3-dipropylxanthine) receptor antagonists fail to increase extracellular dopamine (DA) in the shell of the nucleus accumbens (NAc). However, it has also been reported that caffeine (10 and 30 mg/kg i.p.) and the A1 antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) increases NAc shell DA. To clarify this issue rats were implanted with microdialysis probes at different sites in the NAc shell, in the medial prefrontal cortex (PFCX, infralimbic cortex), and at the border between those areas. Irrespective of probe placement within the NAc shell and of the use of different surgical anesthetics (chloral hydrate and ketamine), we failed to observe changes in dialysate DA after 10 and 30 mg/kg i.p. of caffeine. Similarly negative results were obtained with DPCPX and CPFPX, two potent and selective A1 receptor antagonists. A significant increase of DA was obtained after caffeine when probes were located at the border between the NAc shell and the PFCX (10 and 30 mg/kg) or in the PFCX (10 mg/kg). In view of this and of our previous report that caffeine increases dialysate DA in the medial PFCX, we conclude that the increase in dialysate DA by caffeine observed by others arises from the medial PFCX rather than from the NAc shell as a result of placement of microdialysis probes at the border between the NAc shell and the PFCX. [ABSTRACT FROM AUTHOR]

R,S(±)-3,4-methylenedioxymethamphetamine (R,S(±)-MDMA, ‘Ecstasy’) is known to stimulate dopamine (DA) transmission in the nucleus accumbens (NAc). In order to investigate the post-synaptic correlates of pre-synaptic changes in DA transmission and their relationship with MDMA enantiomers, we studied the effects of R,S(±)-MDMA, S(+)-MDMA, and R(−)-MDMA on extracellular DA and phosphorylated extracellular signal regulated kinase (pERK) in the NAc shell and core. Male Sprague–Dawley rats, implanted with a catheter in the femoral vein and vertical concentric dialysis probes in the NAc shell and core, were administered i.v. saline, R,S(±)-MDMA, S(+)-MDMA, or R(−)-MDMA. Extracellular DA was monitored by in vivo microdialysis with HPLC. Intravenous R,S(±)-MDMA (0.64, 1, and 2 mg/kg) increased dialysate DA, preferentially in the shell, in a dose-related manner. S(+)-MDMA exerted similar effects but at lower doses than R,S(±)-MDMA, while R(−)-MDMA (1 and 2 mg/kg) failed to affect dialysate DA. R,S(±)- and S(+)-MDMA but not R(−)-MDMA increased ERK phosphorylation (expressed as density/neuron and number of pERK-positive neurons/area) in both subdivisions of the NAc. The administration of the D1 receptor antagonist, SCH 39166, prevented the increase in pERK elicited by R,S(±)-MDMA and S(+)-MDMA, while the D2/3 receptor antagonist, raclopride, increased pERK in the NAc core per se but failed to affect the R,S(±)-MDMA-elicited stimulation of pERK. The present results provide evidence that the DA stimulant effects of racemic MDMA are accounted for by the S(+)-enantiomer and that pERK may represent a post-synaptic correlate of the stimulant effect of R,S(±)-MDMA on D1-dependent DA transmission. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*05:02:23 differs from DQB1*05:02:01 by a mutation at nucleotide 450. [ABSTRACT FROM AUTHOR]

Parietal and occipital cortices, while densely innervated by noradrenalin 2 (NA) projections, possess a comparatively sparse dopamine 2 (DA) innervation, even sparser than the prefrontal cortex. We previously reported that reboxetine and desipramine, two selective norepinephrine transporter (NET) blockers, at doses that maximally increase DA in the prefrontal cortex, do not increase DA in the parietal and occipital cortices. In the present study, we performed a full dose–response study of the effect of systemic reboxetine and desipramine on DA and NA in dialysates from the parietal and occipital cortices. Seven doses of reboxetine (0.1, 0.25, 0.5, 1.0, 2.5, 5.0 and 10 mg/kg) and four doses of desipramine (0.25, 1.0, 2.5 and 5.0 mg/kg) were tested. Reboxetine and desipramine differentially affected dialysate DA as compared with NA. Reboxetine increased DA maximally by about 100% after doses of 0.25–0.5 mg/kg and showed a bell-shaped dose–response function in both areas; desipramine did not affect DA in the parietal cortex and increased it in the occipital cortex only at 2.5 mg/kg. NA was maximally increased by 275% by 0.5–2.5 mg/kg reboxetine and by about 300% by 5.0 mg/kg desipramine with a more linear dose–response curve. The mechanism of peculiar dose–response function of dialysate DA after reboxetine and desipramine was further investigated by testing the effect of drugs on dialysate DA and NA under α2 receptor blockade. Under local perfusion of the occipital cortex with idazoxan, an otherwise ineffective dose of reboxetine and desipramine (5 mg/kg) became effective in raising extracellular DA. In contrast, the effect of reboxetine on NA was potentiated, while that of desipramine was not affected. These results suggest that, in the parietal and occipital cortices, extracellular NA, raised by NET blockade, exerts a preferential inhibitory influence on DA release by acting on local α2 receptors, thus accounting for the bell-shaped feature of the dose–response function of drugs on dialysate DA in these areas. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of two serotonin (5-HT) uptake inhibitors, citalopram and paroxetine, and of a non-selective noradrenaline (NA) and 5-HT uptake blocker, imipramine, on extracellular NA and dopamine (DA) in the prefrontal cortex (PfCX), parietal cortex (ParCX) and occipital cortex (OccCX). Citalopram, the most selective 5-HT uptake blocker, increased dialysate DA in the OccCX and ParCX but not in the PfCX and this effect was prevented in the OccCX by WAY-100635, an antagonist of serotonin-1A (5-HT1A) receptors, but not by dorsal noradrenergic bundle (DNAB) lesions that reduced to unmeasurable levels basal dialysate NA but did not affect dialysate DA. Paroxetine, a less selective 5-HT uptake inhibitor than citalopram, at the dose of 5 mg/kg, increased DA in the OccCX but not in the PfCX; however, at doses of 10 mg/kg, which increase PfCX NA, paroxetine increased DA also in this area. Imipramine increased dialysate DA and NA both in the PfCX and in the OccCX and this effect was abolished by DNAB lesions and was reduced but not abolished by WAY-100635. Administration of doses of reboxetine and citalopram that do not increase DA release in the OccCX if given separately, markedly increased DA when combined. These results indicate that endogenous 5-HT, raised by selective blockade of the 5-HT carrier, can increase extracellular DA in the OccCX and in the ParCX by stimulating 5-HT1A receptors independently from the presence of NA terminals, although blockade of 5-HT and NA carrier can strongly interact to raise extracellular DA in this area. These observations are consistent with the existence of DA neurons separate from the NA ones contributing to extracellular DA even in NA-rich/DA poor isocortical areas. [ABSTRACT FROM AUTHOR]

This study compared the interaction between noradrenaline (NA) and dopamine (DA) mechanisms in the prefrontal (PFCX) and in the parietal (ParCX) and occipital (OccCX) cortex. The effect of reboxetine and desipramine, two NA transporter blockers, of mianserin, an antagonist of α2 and 5-HT2 receptors, and of clozapine, an atypical antipsychotic, on dialysate DA in the medial PFCX, ParCX and OccCX was studied. We also assessed the influence of a prior 6-hydroxydopamine (6-OHDA) lesion of the dorsal noradrenergic bundle (DNAB) on the effect of reboxetine and clozapine on dialysate DA in the PFCX and ParCX. Systemic administration of reboxetine and desipramine dose-dependently increased dialysate DA in the PFCX but not in the ParCX and OccCX. In contrast, mianserin and clozapine raised dialysate DA in the ParCX and OccCX to an even larger extent than in the PFCX. 6-OHDA lesions of DNAB abolished the increase of dialysate DA elicited by reboxetine in the PFCX and by clozapine both in the PFCX and in the ParCX. It is concluded that, although PFCX and ParCX/OccCX share the presence of a strong control of DA transmission by NA through α2 receptors, they differ in the extent to which DA is cleared from the extracellular compartment by uptake through the NA transporter. This process, although extensive in the PFCX, appears insignificant in the ParCX and OccCX, probably as a result of the higher ratio of NA to DA resulting in exclusion of DA from NA transporter. [ABSTRACT FROM AUTHOR]

We have recently reported that behavioural sensitization to morphine, amphetamine, cocaine and nicotine is associated with an increased response of dialysate dopamine to the same drugs in the nucleus accumbens core and/or a reduced response in the shell. Prolonged exposure to stressful stimuli also induces behavioural sensitization to drugs of abuse. We therefore investigated the effect of different drugs of abuse on behaviour and on dopamine transmission in the nucleus accumbens shell and core of rats stressed by 1 week schedule of food restriction. Food-restricted rats (80% of their initial body weight) were implanted with microdialysis probes in the nucleus accumbens shell and core and challenged with cocaine (5 and 10 mg/kg i.p.), amphetamine (0.25 and 0.5 mg/kg s.c.), morphine (1 and 2 mg/kg s.c.), nicotine (0.2 and 0.4 mg/kg s.c.) and the changes in dialysate dopamine transmission were monitored together with the behaviour. Food restricted rats showed strong behavioural sensitization to cocaine and amphetamine but not to morphine or nicotine as compared to ad libitum fed controls. Behavioural sensitization to psychostimulants was associated with an increased response of dialysate dopamine in the core and with an unchanged or even reduced response in the shell. No significant differences were observed between controls and food-restricted animals in the ability of morphine and nicotine to stimulate dopamine transmission in the shell and core. The present results indicate that a sensitized dopamine response in the nucleus accumbens core is a general feature of the expression of behavioural sensitization. [ABSTRACT FROM AUTHOR]

The role of dopamine (DA) in associative learning was studied in a conditioned taste aversion (CTA) paradigm with sucrose as the conditioned stimulus (CS) and intraperitoneal lithium chloride as the unconditioned stimulus (US). Drinking on trial of a 15% sucrose solution followed 1 h later by lithium chloride (20 or 40 mg/kg i.p.) resulted in mild CTA, as shown by reduction of drinking of the sucrose solution 24 h later. Amphetamine sulphate (0.125, 0.25, 0.50 and 1.0 mg/kg s.c.), administered on trial 5 min after sucrose drinking, facilitated CTA with maximal effects at 0.25 mg/kg s.c. Amphetamine given in the absence of lithium or 45 min after sucrose did not affect sucrose intake. The DA D1 receptor antagonist SCH 39166, administered before amphetamine either systemically (0.0125 mg/kg s.c.) or in the nucleus accumbens shell (NAc; 0.025 µg/µL on each side) prevented the facilitation of CTA induced by amphetamine. It is concluded that amphetamine facilitates CTA learning by strengthening the consolidation of gustatory short-term memory via D1 receptors of the NAc shell. [ABSTRACT FROM AUTHOR]

Abstract We have previously shown in non-deprived rats that feeding of an unfamiliar palatable food (Fonzies®) phasically stimulates in vivo dopamine (DA) transmission in the medial nucleus accumbens (NAc) and this effect undergoes habituation after a previous (24 h) Fonzies meal (Bassareo & Di Chiara 1997, J. Neurosci., 17, 851–861). The present study shows that an unfamiliar food (Kinder®) with a taste and composition (milk chocolate) different from that of Fonzies, also induces a release of DA in the NAc subjected to one-trial habituation. Habituation was taste specific as no cross-habituation was observed between Fonzies and Kinder. In undeprived rats, a 40-min exposure to an intrinsic appetitive stimulus (food smell arising from a Fonzies-filled plastic box) also prevented the increase in dialysate DA associated with Fonzies feeding, and this effect was partially reversed by food deprivation. Food deprivation also prevented habituation of Fonzies-induced increase of dialysate DA in the NAc. Predictive association of an empty plastic box to Fonzies feeding resulted in the acquisition of appetitive properties by the box and in facilitation (rather than inhibition) of the phasic responsiveness of DA transmission to Fonzies feeding. A 10-min pre-exposure to appetitive olfactory stimuli intrinsic to Fonzies still prevented, like a 40-min pre-exposure, the NAc DA response to Fonzies feeding; however, a 5-min pre-exposure to these appetitive stimuli did not prevent the DA response in the NAc. These results show that the phasic responsiveness of NAc DA transmission to an unfamiliar palatable food is under strong modulatory control by primary (consummatory) and secondary (appetitive) stimuli, and that the sign and extent of this control depends on the nature of the appetitive stimulus, delay of reward and motivational state (deprivation). [ABSTRACT FROM AUTHOR]

We report a case of a seven-yr-old girl with a PAH treated with continuation therapy of bosentan and sildenafil. The combination therapy revealed safety and efficacy in long-term follow up. [ABSTRACT FROM AUTHOR]

With the development of the ICD-11, the debate about classifying certain psychoactive substances such as antidepressant medication and caffeine as drugs of dependence is ignited again. We argue that any coherent theory of addiction needs to identify the neurobiological processes elicited by a potentially addictive substance and to clearly define the clinical symptoms associated with these processes, which can then be used to guide diagnosis. Tolerance development and withdrawal symptoms can occur with any pharmacologically active agent, and their presence is not a sufficient criterion for the clinical diagnosis of an addictive disorder. Drug craving, drug seeking, and drug consumption in spite of harmful consequences are further key criteria for the diagnosis of substance dependence. Even though these symptoms have been associated with dopamine release in the ventral striatum, ventral striatal dopamine release alone is not a sufficient criterion of the addictive property of a drug. For example, common reinforcers such as food and sex increase dopamine transmission in the nucleus accumbens, but unlike in addictive substances, their effect is regulated by reward predictability and habituation. We emphasize the importance to integrate neurobiological as well as behavioral and clinical effects of a substance to assess its addictive liability. We provide a number of widely discussed examples and a list of key criteria as a conceptual guideline for addiction research and clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Non-adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste-related rise and a late rise related to dialysate ethanol. Pre-exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre-exposed group when sucrose-containing ethanol solutions were tested. The results indicate that single trial pre-exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs. [ABSTRACT FROM AUTHOR]

The role of μ[sub 1] opioid receptors in the stimulation of dopamine transmission in the rat nucleus accumbens by an unusual palatable food (Fonzies) and non-psychostimulant drugs of abuse was investigated by the use of naloxonazine, a pseudo-irreversible antagonist of μ[sub 1] opioid receptors. Feeding of Fonzies stimulated dopamine release in the medial prefrontal cortex and in the shell, but not in the core of the nucleus accumbens. Pretreatment with naloxonazine given systemically (15 mg/kg i.p. 20 h before) completely prevented the stimulation of dopamine release in the shell of the nucleus accumbens by Fonzies without affecting that in the prefrontal cortex. Systemic pretreatment with naloxonazine reduced or, depending on the dose, abolished, the stimulation of dopamine release in the nucleus accumbens shell by morphine, nicotine and ethanol, but did not affect that by haloperidol. Naloxonazine also prevented the stimulatory effects of Fonzies, nicotine and morphine on nucleus accumbens dopamine transmission when infused bilaterally in the ventral tegmental area. The results indicate that μ[sub 1] opioid receptors in the ventral tegmentum play a major role in the stimulant effects of food and drugs of abuse on mesolimbic dopamine transmission. [ABSTRACT FROM AUTHOR]

Reticulocyte hemoglobin content (CHr) is considered an index of iron status, helpful in the differential diagnosis of microcytoses. Its potential can be enhanced by comparing CHr dynamic reference values (CHr-e: expected CHr), which are proportional to the MCVr variations occurring in micro- or macrocytosis, with measured CHr values. We demonstrate that the difference between measured CHr and CHr-e (ΔCHr) is helpful to differentiate the anemic syndromes and, in particular, β-talassemia vs. presumable sideropenia. ΔCHr can also indicate when to interrupt iron supplementation. ΔCHr allows an insight into the erythropoiesis of thalassemic and sideropenic subjects, pointing out the reduced hemoglobin production and ineffective erythroid activity in these conditions. [ABSTRACT FROM AUTHOR]