One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial.

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Neuroimaging revealed long-lasting glucose metabolism changes to morphine withdrawal in rats pretreated with the cannabinoid agonist CP-55,940 during periadolescence.

This study evaluates the long-term effects of a six and 14-week morphine withdrawal in rats pretreated with a cannabinoid agonist (CP-55,940, CP) during periadolescence. Wistar rats (33 males; 32 females) were treated with CP or its vehicle (VH) from postnatal day (PND) 28-38. At PND100, rats performed morphine self-administration (MSA, 15d/12 h/session). Eight groups were defined according to pretreatment (CP), treatment (morphine), and sex. Three [18F]FDG-PET brain images were acquired: after MSA, and after six and 14 weeks of withdrawal. PET data were analyzed with SPM12. Endocannabinoid (EC) markers were evaluated in frozen brain tissue at endpoint. Females showed a higher mean number of self-injections than males. A main Sex effect on global brain metabolism was found. FDG uptake in males was discrete, whereas females showed greater brain metabolism changes mainly in areas of the limbic system after morphine treatment. Moreover, the morphine-induced metabolic pattern in females was exacerbated when CP was previously present. In addition, the CP-Saline male group showed reduced CB1R, MAGL expression, and NAPE/FAAH ratio compared to the control group, and morphine was able to reverse CB1R and MAGL expression almost to control levels. In conclusion, females showed greater and longer-lasting metabolic changes after morphine withdrawal than males, indicating a higher vulnerability and a different sensitivity to morphine in subjects pre-exposed to CP. In contrast, males primarily showed changes in EC markers. Together, our results suggest that CP pre-exposure contributes to the modulation of brain metabolism and EC systems in a sex-dependent manner.

Deleterious effects of two pesticide formulations with different toxicological mechanisms in the hepatopancreas of a freshwater prawn.

The aim of this study was to evaluate the acute effects of the pyrethroid cypermethrin (CYP) and the last generation pesticide spirotetramat (STM) on the prawn Macrobrachium borellii. Initially, the 96-h LC50 was determined in adult prawns. Then, prawns were exposed to sublethal concentrations of pesticides (5% and 20% of the 96-h LC50 values) for four days and hepatopancreas were dissected for biomarkers analyses. Total protein and uric acid content, glutathione S-transferase (GST) activity, levels of lipid peroxidation (LPO), and protein oxidation (PO) were evaluated. Additionally, the presence of histopathological changes, lipofuscins, and neutral lipids accumulation were analyzed. The 96-h LC50 values were 0.12 µg/L and 8.2 mg/L for CYP and STM, respectively. The total proteins and uric acid content were not significantly affected by the treatments (p > 0.05). STM significantly affected the GST activity only at the highest concentration (p < 0.001). However, LPO and OP levels were affected by the lowest concentrations of both pesticides (p < 0.003). CYP and STM caused dose-dependent histological damage as was indicated by the histopathological index. The accumulation of lipofuscins showed a dose-dependent response, while the neutral lipids were significantly accumulated in the prawns exposed to the lowest concentration of both pesticides (p < 0.001). The integrated biomarker index (IBRv2) results indicated that the histological parameters represented the most sensitive biomarkers in M. borellii exposed to CYP and STM. Besides, the pyrethroid showed the highest response at concentration ranges that could be present in its natural environments.

3D Synaptic Organization of the Rat CA1 and Alterations Induced by Cocaine Self-Administration.

The hippocampus plays a key role in contextual conditioning and has been proposed as an important component of the cocaine addiction brain circuit. To gain knowledge about cocaine-induced alterations in this circuit, we used focused ion beam milling/scanning electron microscopy to reveal and quantify the three-dimensional synaptic organization of the neuropil of the stratum radiatum of the rat CA1, under normal circumstances and after cocaine-self administration (SA). Most synapses are asymmetric (excitatory), macular-shaped, and in contact with dendritic spine heads. After cocaine-SA, the size and the complexity of the shape of both asymmetric and symmetric (inhibitory) synapses increased but no changes were observed in the synaptic density. This work constitutes the first detailed report on the 3D synaptic organization in the stratum radiatum of the CA1 field of cocaine-SA rats. Our data contribute to the elucidation of the normal and altered synaptic organization of the hippocampus, which is crucial for better understanding the neurobiological mechanisms underlying cocaine addiction.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia.

OBJECTIVE: Treatment resistance is a challenge for the management of schizophrenia. It is not always clear whether inadequate response is secondary to medication ineffectiveness, as opposed to medication underexposure due to non-adherence or pharmacokinetic factors. We investigated the prevalence of subtherapeutic antipsychotic plasma levels in patients identified as treatment-resistant by their treating clinician. METHOD: Between January 2012 and April 2017, antipsychotic plasma levels were measured in 99 individuals provisionally diagnosed with treatment-resistant schizophrenia by their treating clinicians, but not prescribed clozapine. Patients were followed up to determine whether they were subsequently admitted to hospital. RESULTS: Thirty-five per cent of plasma levels were subtherapeutic, and of these, 34% were undetectable. Black ethnicity (P = 0.006) and lower dose (P < 0.001) were significantly associated with subtherapeutic/undetectable plasma levels. Individuals with subtherapeutic/undetectable levels were significantly more likely to be admitted to hospital (P = 0.02). CONCLUSION: A significant proportion of patients considered treatment-resistant have subtherapeutic antipsychotic plasma levels, and this is associated with subsequent admission. The presence of subtherapeutic plasma levels may suggest a need to address adherence or pharmacokinetic factors as opposed to commencing clozapine treatment. While antipsychotic levels are not recommended for the routine adjustment of dosing, they may assist with the assessment of potential treatment resistance in schizophrenia.

Differential response between histological and biochemical biomarkers in the apple snail Pomacea canaliculata (Gasteropoda: Amullariidae) exposed to cypermethrin.

To develop effective programs to monitor water quality is necessary to identify sensitive biomarkers in indicator species. The aim of this study was to evaluate different biomarkers in the apple snail Pomacea canaliculata exposed to the insecticide Cypermethrin (CYP). Adult male and female snails were exposed to sublethal CYP concentrations (10, 25 and 100µgl-1) for 1, 4, 7 and 14days. The recovery of the exposed snails was also studied by a post-exposure assay. The activities of the enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), the levels of lipid peroxidation (LPO) and protein oxidation (PC) in digestive gland and gills were studied as biomarkers of exposure. Histopathological changes in target tissues were also evaluated. In digestive gland, CYP caused a significant increase in SOD, CAT and GST activities compared to control (p<0.05) as well as in LPO and PC levels (p<0.05). However, such biochemical effects were neither concentration nor time dependent. Histopatological changes were observed in the exposed groups, such as an increase in the number of basophilic cells, hemocytic infiltration and epithelia atrophy. Additionally, a positive correlation between the surface occupied by pigmented corpuscles and CYP concentrations was observed at all exposure periods. Gills showed greater sensitivity to oxidative damage than digestive gland. CYP caused an acute toxic effect in LPO levels in this respiratory organ. The gill filament of exposed snails, exhibited a reduction or loss of cilia, vacuolization of the columnar cells and an increase in haemocyte content irrespective of the concentration. High concentrations of CYP caused disruptions in the columnar muscle fibers. In general, snails did not show an improvement in their basal state during post-exposure treatment. Apparently, males and females do not have differential sensitivity to the pesticide. The results of this study suggest that histopathological changes are the most sensitive time- and dose-dependent biomarkers of toxicity induced by CYP in P. canaliculata.

DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia.

Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes. Next, we identified non-coding single-nucleotide polymorphisms (SNPs) associated with co-expression of this pathway. These SNPs were associated with regulatory genetic loci in the dorsolateral prefrontal cortex (P<0.05). We summarized their compound effect on co-expression into a Polygenic Co-expression Index (PCI), which predicted DRD2 pathway co-expression in both mRNA data sets (all P<0.05). We associated the PCI with brain activity during WM performance in two independent samples of healthy individuals (total N=368) and 29 patients with SCZ who performed the n-back task. Greater predicted DRD2 pathway prefrontal co-expression was associated with greater prefrontal activity and longer WM reaction times (all corrected P<0.05), thus indicating inefficient WM processing. Blind prediction of treatment response to antipsychotics in two independent samples of patients with SCZ suggested better clinical course of patientswith greater PCI (total N=87; P<0.05). The findings on this DRD2 co-expression pathway are a proof of concept that gene co-expression can parse SCZ risk genes into biological pathways associated with intermediate phenotypes as well as with clinically meaningful information.

Peripapillary RNFL Thickness Changes Evaluated with Spectral Domain Optical Coherence Tomography after Uncomplicated Macular Surgery for Epiretinal Membrane.

PURPOSE: To evaluate the peripapillary RNFL (p-RNFL) thickness changes after vitrectomy for epiretinal membrane (ERM). The relationship between p-RNFL thickness change and visual function was assessed. METHODS: Thirty-five eyes from 35 patients with ERM who underwent vitrectomy with internal limiting membrane (ILM) removal were included. Average p-RNFL and the four quadrants thickness were measured by spectral-domain optical coherence tomography (SD-OCT) before and at one, three, and six months after surgery. RESULTS: At six months after surgery, p-RNFL thickness of the temporal and inferior quadrant was decreased in the operated eyes compared with fellow eyes (p<0.05). Pattern standard deviation (PSD) was higher than that of fellow eyes (p = 0.002). The temporal and inferior quadrant p-RNFL thickness showed a relationship with both best-corrected visual acuity (BCVA) outcome and the six-month PSD (p<0.05, respectively). CONCLUSIONS: The selective decrease in the temporal and inferior p-RNFL thickness after vitrectomy for ERM removal could indicate inner retinal damage related to ILM peeling.

Changes in D1 but not D2 dopamine or mu-opioid receptor expression in limbic and motor structures after lateral hypothalamus electrical self-stimulation: A quantitative autoradiographic study.

Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH) is involved in the activation of neuroanatomical systems that are also associated with the processing of natural and other artificial rewarding stimuli. Specific components of this behavior (hedonic impact, learning, and motor behavior) may involve changes in different neurotransmitters, such as dopamine and opioids. In this study, quantitative autoradiography was used to examine changes in mu-opioid and D1/D2-dopamine receptor expression in various anatomical regions related to the motor and mesolimbic reward systems after intracranial self-stimulation of the LH. Results of the behavioral procedure and subsequent radiochemical assays show selective changes in D1 but not D2 or mu receptors in Accumbens-Shell, Ventral Pallidum, Caudate-Putamen, and Medial Globus Pallidus. These findings are discussed in relation to the different psychobiological components of the appetitive motivational system, identifying some dissociation among them, particularly with respect to the involvement of the D1-dopamine subsystem (but not D2 or mu receptors) in goal-directed behaviors.

[The bilateral renal lymphoma: an incurable disease? Case report]. / Il linfoma renale bilaterale: è ancora una malattia incurabile? Case Report.

The bilateral primary renal lymphoma (PRL) is a rare disease with a high mortality rate (75% within the first year). We report the case of a fifty-three years old women observed in January 2011 for renal colic. Ultrasonography showed hypoechoic lobular formations in the kidney. Blood tests showed: creatinine 1.8 mg/dl, urea 75 mg/dl , Creatinine Clerance 35 ml/m, hemoglobinemia 11 g/dl, with blood cells 8.500/mcL, Albumin 2.8 g/dl, Beta -2 micro - 27.3/mL. Proteinuria was 0.3 g/24 hours. The CT scan showed kidneys with larger dimensions and multiple hypodense areas infiltrating the renal parenchyma with contrast-enhanced low in which kidneys had lesions similar to "leopard skin". The CT scan showed no enlarged lymph nodes. Renal biopsy showed: renal parenchyma largely occupied by infiltration of lymphoid elements, small and medium-sized, densely packed with compression of the tubular structures . Immunofluorescence for immunoglobulin (Ig) G, IgA, IgM, C3, C4, C1q, fibrinogen, kappa and lambda were negative. The bone marrow biopsy excluded lymphomatous infiltration. The histological diagnosis was "non-Hodgkin's B-cell lymphoma"; the clinical diagnosis was LRBP. The patient was treated by 6 cycles of R-CHOP-21 protocol (rituximab - endoxan, adriblastina , vincristine, prendnisone), the latter of which practiced in August 2011. The pt is currently in follow-up hematology and nephrology . The first TAC control , in October 2011, showed a complete regression of the lesions infiltrating . This finding was confirmed by two other CT scan performed in February and October 2012. The last blood tests of February 2013 showed : creatinine 1.1 mg / dl , Urea 40 mg/dl, proteinuria absent. Currently, the pt is asymptomatic and is being treated by low dose of ACE inhibitor. The bilateral PRL is considered a severe disease with one-year mortality of 75% . The successful outcome of the case described can be attributed to haematological therapy and to the early diagnosis.

Cocaine facilitates protein synthesis-dependent LTP: the role of metabotropic glutamate receptors.

Cocaine addiction alters synaptic plasticity in many brain areas involved in learning and memory processes, including the hippocampus. Long-term potentiation (LTP) is one of the best studied examples of hippocampal synaptic plasticity and it is considered as one of the molecular basis of learning and memory. We previously demonstrated that in the presence of cocaine, a long lasting form of hippocampal LTP is induced by a single pulse of high frequency stimulation, which in normal conditions evokes only an early form of LTP. In this study, we further explore the molecular basis of this modulation of synaptic plasticity by cocaine. By performing pharmacological experiments on hippocampal slices, we were able to show that cocaine converts early LTP to a form of LTP dependent on protein synthesis, probably through the cAMP-dependent protein kinase and extracellular signal-regulated kinase signaling cascades. We also found that metabotropic glutamate receptors are involved in this phenomenon. These studies further clarify the molecular machinery used by cocaine to alter synaptic plasticity and modulate learning and memory processes.

Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

BACKGROUND: Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. METHOD: We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. RESULTS: Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. CONCLUSIONS: Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

Ocular traumatology in children. A retrospective study.

UNLABELLED: OBIECTIVE: This study assesses the descriptive epidemiology of children with eye injuries presenting to the Emergency Department of a non exclusive Paediatric University Hospital - First Division of Ophthalmology of "Sapienza" University of Rome - over a period of 12 years. STUDY DESIGN: A retrospective long term study of 12 years. PARTICIPANTS: All paediatric patients (up to 14 years of age) presenting with ocular injuries and hospitalized. METHODS: It was analyzed the incidence of the ocular trauma among males and females. The situation in which the trauma occurred, type of trauma (contusive or perforating), the presence of endo-bulbar foreign bodies, visual acuity outcome. RESULTS: There were 203 patients who presented to the Emergency Department in the period examined. Contusive traumas were 130 (90 males, 40 females). The perforating trauma were 73 (63 males, 10 females). The presence of an endo-bulbar foreign body was registered in 10 patients. A detailed analysis of the causes of the trauma is therefore provided. We evidence that males were almost exclusively involved in sport traumas (60 males versus 2 females), and in second instance accidental trauma is almost equally divided between two genders. CONCLUSIONS: Our retrospective study presents the paediatric cases of a non exclusive Paediatric University Hospital where 3% of ocular traumas requiring hospitalization were in children. Therefore our data could be useful in order to bring about the necessary preventive measures to minimize paediatric eye injuries.

Costs and consequences of acupuncture as a treatment for chronic pain: a systematic review of economic evaluations conducted alongside randomised controlled trials.

BACKGROUND: The economic burden that chronic pain conditions impose on individuals and society is significant. Acupuncture appears to be a clinically effective treatment for some chronic pain conditions. Given the need for policy decisions to be informed by economic evaluations, the objective of this systematic review was to synthesise data from economic evaluations to determine whether acupuncture for the treatment of chronic pain conditions is good value for money. METHODS: A literature search was conducted using health and economics databases, with additional hand-searching. Economic evaluations conducted alongside randomised controlled trials were eligible. RESULTS: Eight economic evaluations were included in this review, seven cost-utility analyses and one cost-effectiveness analysis. Conditions treated included low back pain, neck pain, dysmenorrhoea, migraine and headache, and osteoarthritis. From the seven cost-utility analyses, acupuncture was found to be clinically effective but cost more. The cost per quality adjusted life year (QALY) gained ranged from £2527 to £14,976 per QALY, below the commonly quoted threshold used by the UK National Institute for Health and Clinical Excellence of £20,000 to £30,000. The one cost-effectiveness study indicated that there might be both clinical benefits and cost savings associated with acupuncture for migraine. There was heterogeneity across the eight trials in terms of professional who provided the acupuncture, style of acupuncture, and country of origin. CONCLUSION: The cost per QALY gained in all seven cost-utility studies was found to be below typical thresholds of willingness to pay. Acupuncture appears to be a cost-effective intervention for some chronic pain conditions.

Differential gene expression in the nucleus accumbens and frontal cortex of lewis and Fischer 344 rats relevant to drug addiction.

Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism.These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse.

Depotentiation of hippocampal long-term potentiation depends on genetic background and is modulated by cocaine self-administration.

Lewis (LEW) and Fischer 344 (F344) rats differ in their response to drugs and are frequently used as an experimental model to study vulnerability to drug addiction. We have previously reported that significant differences in hippocampal synaptic plasticity exist between LEW and F344 rats after non-contingent chronic cocaine administration. However, given the several biochemical differences between contingent and non-contingent administration of drugs, we have studied here the possible genetic differences in synaptic plasticity after contingent cocaine self-administration. LEW and F344 animals self-administered cocaine (1 mg/kg i.v.) or saline under a fixed ratio 1 schedule of reinforcement for 20 days. After self-administration, electrophysiological experiments were carried out in which hippocampal slices were tetanized with three high frequency pulses in order to induce long-term potentiation (LTP). After a 20 min period of LTP stabilization, a train of low frequency stimulation (LFS; 900 pulses, 1 Hz) was applied to induce depotentiation of LTP. Data showed no differences between cocaine self-administered LEW or F344 rats in the induction of saturated-LTP compared to saline animals. LEW saline self-administered rats showed normal LTP depotentiation whereas cocaine self-administration impaired depotentiation in this rat strain. In the F344 strain, depotentiation of saturated-LTP was impaired both in saline and cocaine self-administered rats. The present results corroborate previous findings showing differences in basal hippocampal synaptic plasticity between LEW and F344 rats. These differences seem to modulate cocaine effects in a manner independent of contingency of drug administration.

Chronic periadolescent cannabinoid treatment enhances adult hippocampal PSA-NCAM expression in male Wistar rats but only has marginal effects on anxiety, learning and memory.

Pubertal and adolescent exposure to cannabinoids is associated with enduring alterations in anxiety and memory. However, periadolescence virtually remains unexplored. Here, we measured anxiety in the Elevated Plus Maze (EPM) in adult Wistar rats treated at periadolescence (P28-P38) with the cannabinoid agonist CP 55,940 (CP) (0.4 mg/kg; 2 ml/kg i.p., 1 daily injection), and we also defined their recognition memory in the novel object paradigm and spatial learning and memory in the water maze. Additionally, we measured the expression of hippocampal PSA-NCAM (Polysialic Acid-Neural Cell Adhesion Molecule) and long-term potentiation (LTP) as well as, given their role in mnemonic processing, the levels of plasma corticosterone and estradiol. We found that CP had no robust effects on anxiety or in recognition memory. In the water maze, only a slight decreased percentage of failed trials in the reference memory task and an improvement in an indirect index of attention were observed. However, we detected an up-regulation of hippocampal PSA-NCAM expression, only in CP-males, although this effect was not related to changes in LTP. No hormonal alterations were evident. Based on our data, minimal long-term effects on anxiety, learning and memory appear to result from cannabinoid exposure during the periadolescent period.

Genetic differences in hippocampal synaptic plasticity.

Synaptic plasticity is considered a physiological substrate for learning and memory [Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84:87-136] that contributes to maladaptive learning in drug addiction [Schoenbaum G, Roesch MR, Stalnaker TA (2006) Orbitofrontal cortex, decision-making and drug addiction. Trends Neurosci 29:116-124]. Many studies have revealed that drug addiction has a strong hereditary component [Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69; Uhl GR (2004) Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology 47 (Suppl 1):140-147], however the contribution of the genetic background to drug-induced changes in synaptic plasticity has been scarcely studied. The present study reports on an analysis of long-term potentiation (LTP) and depotentiation in Lewis (LEW) and Fischer-344 (F344) rats, two inbred rat strains that show different proneness to drugs of abuse and are considered an experimental model of genetic vulnerability to addiction [Kosten TA, Ambrosio E (2002) HPA axis function and drug addictive behaviors: insights from studies with Lewis and Fischer 344 inbred rats. Psychoneuroendocrinology 27:35-69]. The induction of saturated-LTP was similar in LEW and F344 rats treated with saline or cocaine. However, only slices from LEW saline-treated rats showed the reversal of LTP; thus, the depotentiation of saturated-LTP was not observed in cocaine-injected LEW rats and in F344 animals (treated either with cocaine or saline). These results suggest significant differences in hippocampal synaptic plasticity between Lewis and Fischer 344 rats.