Pomalidomide in heavily pretreated refractory multiple myeloma: a case report.

We present the case of a 70-year-old man diagnosed with multiple myeloma in 2008, who after four therapy lines initiated a fifth-line treatment with pomalidomide (4 mg orally, days 1-21 of a 28-day cycle) and low-dose dexamethasone (40 mg weekly orally). The patient was treated with pomalidomide for almost 2 years achieving a complete remission after 12 cycles. Complete remission was maintained for 9 months. This case illustrates the potential of pomalidomide plus low-dose dexamethasone to overcome multiple myeloma refractoriness inducing a quick and very prolonged remission.

Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies.

The genome-wide distribution of linkage disequilibrium (LD) determines the strategy for selecting markers for association studies, but it varies between populations. We assayed LD in large samples (200 individuals) from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22. Most isolates show substantially higher levels of LD than the outbred sample and many fewer regions of very low LD (termed 'holes'). Young isolates known to have had relatively few founders show particularly extensive LD with very few holes; these populations offer substantial advantages for genome-wide association mapping.

The impact of insularity on SARS-CoV-2 diffusion: Recapitulating three years of COVID-19 pandemic in the island of Sardinia.

BACKGROUND: Italy has been the first European Country dealing with SARS-CoV-2, whose diffusion on the territory has not been homogeneous. Among Italian regions, Sardinia represented one of the lowest incidence areas, likely due to its insular nature. Despite this, the impact of insularity on SARS-CoV-2 genetic diversity has not been comprehensively described. METHODS: In the present study, we performed the high throughput sequencing of 888 SARS-CoV-2 genomes collected in Sardinia during the first 23 months of pandemics. In addition, 1439 high-coverage SARS-CoV-2 genomes circulating in Sardinia along three years (December 2019 - January 2023) were downloaded from GISAID, for a total of 2327 viral sequences that were characterized in terms of phylogeny and genomic diversity. RESULTS: Overall, COVID-19 pandemic in Sardinia showed substantial differences with respect to the national panorama, with additional peaks of infections and uncommon lineages that reflects the national and regional policies of re-opening and the subsequent touristic arrivals. Sardinia has been interested by the circulation of at least 87 SARS-CoV-2 lineages, including some that were poorly represented at national and European level, likely linked to multiple importation events. The relative frequency of Sardinian SARS-CoV-2 lineages has been compared to other Mediterranean Islands, revealing a unique composition. CONCLUSIONS: The genomic diversity of SARS-CoV-2 in Sardinia has been shaped by a complex interplay of insular geography, low population density, and touristic arrivals, leading on the one side to the importation of lineages remaining rare at the national level, and resulting on the other side in the delayed entry of otherwise common variants.

Household contact with pets and birds and risk of lymphoma.

BACKGROUND: Contact with household pets has been suggested to be inversely associated with lymphoma risk. METHODS: We tested the hypothesis in a case-control study of lymphoma in the Sardinia region of Italy. Cases were 326 patients, first diagnosed with lymphoma in 1999-2003. Controls were 464 population controls, frequency matched to cases by age, gender, and area of residence. In person interviews included self-reported household contact with pets and birds, type of pet(s), and age at starting contact. RESULTS: Frequent contact with birds was inversely associated with lymphoma, and particularly B-cell non-Hodgkin lymphoma (odds ratio [OR] = 0.6, 95% confidence interval [95% CI]: 0.4, 0.9). Contact with chickens accounted for this inverse association, which was strongest for first contact occurring at age ≤8 years (OR = 0.4, 95% CI: 0.2, 1.0). No association was observed when first contact occurred at age 9 or older. Contact with any pets was inversely associated with risk of diffuse large B-cell lymphoma (OR = 0.4, 95% CI: 0.2, 1.0), but not other lymphoma subtypes. CONCLUSION: Our results support the hypothesis that early-life exposure to pets, birds and particularly with chickens might be associated with a reduced risk of lymphoma.

Molecular Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Isolates From Central Inner Sardinia.

BACKGROUND: The SARS-CoV-2 pandemic stimulated an outstanding global sequencing effort, which allowed to monitor viral circulation and evolution. Nuoro province (Sardinia, Italy), characterized by a relatively isolated geographical location and a low population density, was severely hit and displayed a high incidence of infection. METHODS: Amplicon approach Next Generation Sequencing and subsequent variant calling in 92 respiratory samples from SARS-CoV-2 infected patients involved in infection clusters from March 2020 to May 2021. RESULTS: Phylogenetic analysis displayed a coherent distribution of sequences in terms of lineage and temporal evolution of pandemic. Circulating lineage/clade characterization highlighted a growing diversity over time, with an increasingly growing number of mutations and variability of spike and nucleocapsid proteins, while viral RdRp appeared to be more conserved. A total of 384 different mutations were detected, of which 196 were missense and 147 synonymous ones. Mapping mutations along the viral genome showed an irregular distribution in key genes. S gene was the most mutated gene with missense and synonymous variants frequencies of 58.8 and 23.5%, respectively. Mutation rates were similar for the S and N genes with one mutation every ∼788 nucleotides and every ∼712 nucleotides, respectively. Nsp12 gene appeared to be more conserved, with one mutation every ∼1,270 nucleotides. The frequency of variant Y144F in the spike protein deviated from global values with higher prevalence of this mutation in the island. CONCLUSION: The analysis of the 92 viral genome highlighted evolution over time and identified which mutations are more widespread than others. The high number of sequences also permits the identification of subclusters that are characterized by subtle differences, not only in terms of lineage, which may be used to reconstruct transmission clusters. The disclosure of viral genetic diversity and timely identification of new variants is a useful tool to guide public health intervention measures.

Adolescent cannabis exposure increases heroin reinforcement in rats genetically vulnerable to addiction.

On the basis of epidemiological studies it has been proposed that cannabis use plays a causal role in the abuse of highly addictive drugs (Gateway Hypothesis). However, epidemiological studies are intrinsically unable to provide evidence of causality. Experimental studies can provide this evidence but they are feasible only in animal models and to date such evidence is lacking. In view of the importance of genetic factors in drug abuse, we investigated the influence of adolescent cannabis exposure on adult heroin reinforcement in two inbred rat strains differentially vulnerable to drugs of abuse, addiction prone Lewis (LEW) and addiction resistant Fischer 344 (F344) strains. Male LEW and F344 rats aged six weeks were exposed to increasing Δ9-tetrahydrocannabinol (THC) doses, twice a day for 3 days (2, 4, 8 mg/kg, i.p.). At adulthood they were allowed to self-administer heroin (0.025 mg/kg) under both Fixed- (FR) and Progressive- (PR) ratio schedules of responding. Following extinction, responding was reinstated by drug-cues and/or by heroin priming. THC pre-exposure increased responding for heroin and heroin intake under FR-3 and FR-5 as well as PR protocols and increased breaking point in PR schedules in LEW but not F344 rats. Drug cues and heroin priming reinstated responding in LEW and F344, but THC pre-exposure increased reinstatement by priming in LEW rats and by cues in F344 rats. These observations show that in genetically predisposed individuals, adolescent cannabis exposure increases heroin reinforcing properties, thus providing a mechanism for a causal role of adolescent cannabis use in heroin abuse.

Early Diffusion of SARS-CoV-2 Infection in the Inner Area of the Italian Sardinia Island.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the coronavirus disease 2019 (COVID-19) pandemic, which started as a severe pneumonia outbreak in Wuhan, China, in December 2019. Italy has been the first European country affected by the pandemic, registering a total of 300,363 cases and 35,741 deaths until September 24, 2020. The geographical distribution of SARS-CoV-2 in Italy during early 2020 has not been homogeneous, including regions severely affected as well as administrative areas being only slightly interested by the infection. Among the latter, Sardinia represents one of the lowest incidence areas likely due to its insular nature. METHODS: Next-generation sequencing of a small number of complete viral genomes from clinical samples and their virologic and phylogenetic characterization was performed. RESULTS: We provide a first overview of the SARS-CoV-2 genomic diversity in Sardinia in the early phase of the March-May 2020 pandemic based on viral genomes isolated in the most inner regional hospital of the island. Our analysis revealed a remarkable genetic diversity in local SARS-CoV-2 viral genomes, showing the presence of at least four different clusters that can be distinguished by specific amino acid substitutions. Based on epidemiological information, these sequences can be linked to at least eight different clusters of infection, four of which likely originates from imported cases. In addition, the presence of amino acid substitutions that were not previously reported in Italian patients has been observed, asking for further investigations in a wider population to assess their prevalence and dynamics of emergence during the pandemic. CONCLUSION: The present study provides a snapshot of the initial phases of the SARS-CoV-2 infection in inner area of the Sardinia Island, showing an unexpected genomic diversity.

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population.

BACKGROUND: In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. METHODS: Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. RESULTS AND CONCLUSION: Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.

Risk of malignant lymphoma following viral hepatitis infection.

We investigated lymphoma risk following hepatitis infection in a case-control study of 274 incident lymphoma cases, defined according to the WHO classification, and 336 population controls in Sardinia, Italy. Part of our study population (198 cases and 219 controls) was included in the EPILYMPH study of Hepatitis C virus (HCV) infection in relation to non-Hodgklin's lymphoma risk. Based on questionnaire information on whether and at what age a diagnosis of hepatitis was posed by a physician, systematic anti-HCV antibodies testing in cases and controls by enzyme-linked immunoassay, and HCV-RNA assessment by PCR analyses in positive samples, we investigated more in detail whether hepatitis non-C is also associated with lymphoma risk, and whether risk varies by clinical form of hepatitis (acute or chronic infection). After adjusting by age, gender, education, and area of birth whether from the study area or elsewhere in Italy, a previous generic diagnosis of hepatitis was associated with a significantly elevated lymphoma risk [odds ratio (OR) = 1.8; 95% CI 1.1, 2.8], which was equally increased for hepatitis B (OR = 1.8; 95% CI 0.9, 3.5), for HCV positive subjects overall (OR = 2.0; 95% CI 0.8, 4.8), and for hepatitis non-B non-C (OR = 1.6; 95% CI 0.7, 3.9). Once concurrent infection from other hepatitis viruses was excluded, acute or chronic hepatitis C was the only one showing a consistent risk increase in all lymphoma subtypes, but follicular lymphoma. Some indications of an excess risk of lymphoma were observed also for acute, but not chronic forms of hepatitis B and hepatitis non-B, non C. Self-limited hepatitis C did not show an association. No significant heterogeneity in the risk of major lymphoma subtype was observed. Our results confirm a role of either acute or chronic active HCV infection in lymphomagenesis. Further studies are warranted to test the hypothesis that acute infection from other hepatitis viruses might also increase lymphoma risk.

The Roman high- and low-avoidance rats differ in the sensitivity to shock-induced suppression of drinking and to the anxiogenic effect of pentylenetetrazole.

The Roman high- (RHA) and low-avoidance (RLA) outbred rat lines are selected for respectively rapid vs. poor acquisition of active avoidant behavior. Emotional reactivity appears to be the most prominent behavioral difference between the two lines, with RLA rats being more fearful/anxious than their RHA counterparts. Accordingly, here we show that shock-induced inhibition of drinking behavior in the Vogel's test is significantly more pronounced in RLA than RHA rats. Thus, unpunished drinking activity is similar in both lines (38.1 ±â€¯0.9 and 36.4 ±â€¯0.6 licking periods/3 min in RLA and RHA rats, respectively), whereas under punished conditions (0.05-1.00 mA electric shocks delivered through the drinking tube) a more robust decrease in drinking behavior is observed in RLA vs. RHA rats. Moreover, fear-related behaviors like freezing and self-grooming are more frequent in RLA than RHA rats throughout the test. Similar results are obtained with the inbred RHA-I and RLA-I rats, which have been selected and bred through brother/sister mating of the outbred lines. In keeping with the above findings, we also show that, compared with their RHA counterparts, the outbred RLA rats are similarly responsive to the anticonflict effect of diazepam but more responsive to the proconflict effect of pentylenetetrazole in the Vogel's test. Collectively, these results reveal another behavioral trait distinguishing RHA from RLA rats and add experimental support to the view that the Roman lines/strains are a valid genetic model for the study of the neural underpinnings of fear/anxiety- and stress-related behaviors.

The psychogenetically selected Roman high- and low-avoidance rat lines: a model to study the individual vulnerability to drug addiction.

The Roman high- (RHA) and low-avoidance (RLA) rat lines were selected for, respectively, rapid vs poor acquisition of two-way active avoidance in the shuttle-box. Here, we review experimental evidence indicating that, compared with their RLA counterparts, RHA rats display a robust sensation/novelty seeking profile, a marked preference and intake of natural or drug rewards, and more pronounced behavioral and neurochemical responses to the acute administration of morphine and psychostimulants. Moreover, we show that (i) the repeated administration of morphine and cocaine elicits behavioral sensitization in RHA, but not RLA, rats, (ii) in sensitized RHA rats, acute morphine and cocaine cause a larger increment in dopamine output in the core, and an attenuated dopaminergic response in the shell of the nucleus accumbens, as compared with RHA rats repeatedly treated with saline, and (iii) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant RLA line. Behavioral sensitization plays a key role in several cardinal features of addiction, including drug craving, compulsive drug seeking and propensity to relapse following detoxification. Comparative studies in the Roman lines may therefore represent a valid approach to evaluate the contribution of the genotype on the neural substrates of drug sensitization and addiction.

Effect of urban traffic, individual habits, and genetic polymorphisms on background urinary 1-hydroxypyrene excretion.

PURPOSE: Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs) and genetic polymorphisms were investigated in relation to their contribution to interindividual variation in baseline levels of urinary 1-hydroxypyrene (1-OHP) excretion in subjects without occupational exposure to PAHs. METHODS: Urinary excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men. Questionnaire information was collected on possible environmental and individual sources of PAH exposure. A subset of 70 individuals also was evaluated for a single-nucleotide polymorphism (Ex7+295C-->T) in the cytochrome P-450 1A2 (CYP1A2) gene, and 61 of these also were evaluated for the glutathione transferase T1 (GSTT1) gene polymorphism. RESULTS: 1-OHP values did not show a significant seasonal variability and were unaffected by age; education; body mass index; smoking status, including passive smoking; or the C-->T base substitution in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9; 95% confidence interval, 1.0-24.9), and frequent intake of grilled meat (odds ratio, 6.9; 95% confidence interval, 1.1-43.5) were significant predictors of background urinary 1-OHP levels of 0.50 microg/g creatinine or greater. Elevated risks also were associated with daily alcohol intake greater than 65 g and the nonnull GSTT1 genotype. CONCLUSION: Our study shows that exposure to urban traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to interindividual variation in background levels of 1-OHP urinary excretion in subjects without occupational exposure to PAHs.

Identification of a founder BRCA2 mutation in Sardinian breast cancer families.

The population of Sardinia is characterized by a relatively low level of genetic heterogeneity: therefore 'founder mutations' can be expected to be found. We analysed 17 probands from families with high incidence of breast cancer or breast and ovarian cancer by sequencing the full-length coding regions of BRCA1 and BRCA2 genes. A novel BRCA2 frame-shift mutation, 3951del3insAT, which produces a protein truncated at codon 1258, was observed in six patients with BC from the same village. The mutation was not found in unaffected females (matched on basis of ethnicity and age) with no family history of cancer. Haplotype analysis strongly suggests that all affected persons had a common ancestor. The identification of this clinically significant founder mutation may facilitate screening/testing for inherited risk of breast cancer.

Neonatal ventral hippocampal lesions potentiate amphetamine-induced increments in dopamine efflux in the core, but not the shell, of the nucleus accumbens.

BACKGROUND: In rats, neonatal ventral hippocampal lesions (NVHLs) result in the postpubertal emergence of alterations reminiscent of several features of schizophrenia, including increased responsivity to the behavioral effects of amphetamine (AMPH). The precise nature of presynaptic aspects of accumbal dopamine (DA) function in these alterations is however uncertain: previous studies have found that the exacerbated responses to AMPH of NVHL rats are associated with either decreased or unchanged DA efflux in the nucleus accumbens (NAc) as compared with shams. Because these studies investigated DA output in the whole NAc, it was considered of interest to examine the impact of NVHLs on DA transmission in NAc subregions involved in distinct aspects of goal-directed behavior. METHODS: The effects of AMPH (.25 mg/kg, subcutaneous) on the accumbal DA efflux of adult rats were evaluated using brain microdialysis, and motor activity was recorded alongside dialysate sample collection. RESULTS: The enhanced behavioral responsivity to AMPH of NVHL rats is associated with potentiation of AMPH-induced DA output in the NAc core and a concomitant attenuation of DA overflow in the NAc shell. CONCLUSIONS: The functional alterations in the NAc core induced by NVHLs provide a link between the hippocampal damage and striatal DA hyperactivity in schizophrenia.

Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value.

RATIONALE: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. OBJECTIVES: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. METHODS: In naïve rats, we assessed (1) the ability of the cocaine (0.250-0.125 mg/kg/infusion) and caffeine (0.125-0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. RESULTS: Cocaine combined with caffeine and cocaine alone was self-administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self-administration behavior in naïve rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. CONCLUSIONS: Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs.

A survey on lifestyle and level of biomarkers of environmental exposure in residents in Civitavecchia (Italy).

BACKGROUND: The assessment of individual exposure to toxicants in industrially contaminated areas is difficult when multiple productions are active close to residential areas. Two thermoelectric power plants and a large harbor have been operating since the '60s in the area of Civitavecchia (North of Rome). METHODS: The ABC (Ambiente e Biomonitoraggio nell'area di Civitavecchia, Environment and Biomonitoring in Civitavecchia) program involved, in the period 2013-2014, residents in Civitavecchia and in the nearby municipalities (Santa Marinella, Allumiere, Tolfa and Tarquinia). They were randomly selected from the Municipal Register's data and their residence addresses were geocoded using GIS techniques. Biomonitoring of the following urinary metals, Sb, Be, Mo, Cd, Sn, W, Ir, Pt, Hg, Tl, V, Cr, Mn, Co, Ni, Cu, Zn, Rh, Pd, As were performed. Glucose and lipid metabolism, liver, renal, and endocrine function were evaluated through blood laboratory tests. Tests of lung functionwere also carried out as well as saturometry (oxygen rate in the blood with an illuminated sensor placed on the fingertip), anthropometric and blood pressure measurements. Information on individual characteristics, histories of exposure, such as the consumption of local food, occupational history, lifestyle and medical history were collected through a validated questionnaire. Samples of nails and hair were also collected. The biological material (blood, urine, nails and hair) was stored in a biobank for future analysis related to the possible mechanisms of biological damage. The study protocol received the approval of the local ethics committee. RESULTS: A total of 1177 residents were enrolled (58% female, 60% with a secondary or graduate school degree). No particular differences in metal concentrations based on the municipality of residence were observed. For arsenic, mercury, lead, and tungsten some differences between the two geographical areas were observed, probably due to different diet, lifestyle (e.g., alcohol consumption, smoking, use of jewelry and piercings, tattoos, physical activity, hormonal and mineral supplements, and drugs), and occupational exposure. CONCLUSIONS: The undergoing study on the association between biomarkers concentration and pollutants concentrations - estimated using a dispersion modeling approach, and adjusting for personal characteristics and concomitant other environmental exposure - could clarify the individual exposure of the residents in this industrial area.

Behavioural effects of acute and repeated cocaine treatments: a comparative study in sensitisation-prone RHA rats and their sensitisation-resistant RLA counterparts.

RATIONALE: Dopamine (DA) transmission is critically involved in the motor effects of psychostimulants and opiates, as well as in the augmentation of these effects resulting from repeated drug administration-a process termed behavioural sensitisation. The latter is known to play a central role in the development and maintenance of drug addiction as well as in the high frequency of relapse observed in drug addicts following detoxification. The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for extreme performances in the acquisition of avoidant behaviour has generated two phenotypes that differ in the functional properties of the mesocortical and mesolimbic DA systems and in their behavioural and neurochemical responses to the acute administration of psychostimulants and opiates. More recently, we showed that repeated morphine or amphetamine injections induce behavioural sensitisation in RHA, but not RLA, rats. OBJECTIVE: To further characterize the differences in the susceptibility to develop psychostimulant sensitisation between the Roman lines, we evaluated the behavioural effects of acute cocaine (5 and 10 mg kg(-1), i.p.) 1 day before and 8 days after repeated administration of saline (2 ml kg(-1), i.p.) or cocaine (10 mg kg(-1), i.p. for 14 consecutive days). RESULTS: We show that repeated cocaine administration elicits augmented behavioural responses to both challenge doses of the same drug only in RHA rats. CONCLUSIONS: The Roman lines represent a useful model to investigate how, and to what extent, the genetic make-up influences the neural substrates of individual vulnerability to addiction.

The psychogenetically selected Roman rat lines differ in the susceptibility to develop amphetamine sensitization.

The mesolimbic dopamine system is considered to play a pivotal role in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration, a process denominated behavioral sensitization. The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats, respectively, for rapid versus poor active avoidance acquisition has resulted in two phenotypes that differ in the functional properties of the mesolimbic dopamine system and in their behavioral and neurochemical responses to addictive drugs, including psychostimulants and opiates. Hence, the present study was designed to compare the ability of these lines to develop behavioral sensitization to psychostimulants. To this aim, the acute effects of amphetamine (0.125 or 0.25 mg/kg, s.c.) on locomotion were assessed in RHA and RLA rats prior to and subsequent to 10 daily doses of either amphetamine (1 mg/kg, s.c.) or saline (1 ml/kg, s.c.). In the RHA line, the locomotor activation produced by either challenge dose of amphetamine was more pronounced in rats that had been repeatedly treated with amphetamine versus the respective saline treated controls. In contrast, no significant change in locomotor activity was observed in RLA rats. Likewise, repeated amphetamine caused an increased frequency of sniffing, rearing, licking/gnawing, and grooming versus the control, repeated saline, group only in the RHA line. The results show that the repeated treatment regimen used in this study induced behavioral sensitization to amphetamine in RHA rats, but not in their RLA counterparts, and underscore the utility of these lines for studying the influence of neural substrates and genetic make up on the individual vulnerability to addiction.