Central and Peripheral Inflammation: A Common Factor Causing Addictive and Neurological Disorders and Aging-Related Pathologies.

Many diseases and degenerative processes affecting the nervous system and peripheral organs trigger the activation of inflammatory cascades. Inflammation can be triggered by different environmental conditions or risk factors, including drug and food addiction, stress, and aging, among others. Several pieces of evidence show that the modern lifestyle and, more recently, the confinement associated with the COVID-19 pandemic have contributed to increasing the incidence of addictive and neuropsychiatric disorders, plus cardiometabolic diseases. Here, we gather evidence on how some of these risk factors are implicated in activating central and peripheral inflammation contributing to some neuropathologies and behaviors associated with poor health. We discuss the current understanding of the cellular and molecular mechanisms involved in the generation of inflammation and how these processes occur in different cells and tissues to promote ill health and diseases. Concomitantly, we discuss how some pathology-associated and addictive behaviors contribute to worsening these inflammation mechanisms, leading to a vicious cycle that promotes disease progression. Finally, we list some drugs targeting inflammation-related pathways that may have beneficial effects on the pathological processes associated with addictive, mental, and cardiometabolic illnesses.

Effects of Early Life Exposure to Sex Hormones on Neurochemical and Behavioral Responses to Psychostimulants in Adulthood: Implications in Drug Addiction.

Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.

Study of the release of endogenous amines in Drosophila brain in vivo in response to stimuli linked to aversive olfactory conditioning.

A highly challenging question in neuroscience is to understand how aminergic neural circuits contribute to the planning and execution of behaviors, including the generation of olfactory memories. In this regard, electrophysiological techniques like Local Field Potential or imaging methods have been used to answer questions relevant to cell and circuit physiology in different animal models, such as the fly Drosophila melanogaster. However, these techniques do not provide information on the neurochemical identity of the circuits of interest. Different approaches including fast scan cyclic voltammetry, allow researchers to identify and quantify in a timely fashion the release of endogenous neuroactive molecules, but have been only used in in vitro Drosophila brain preparations. Here, we report a procedure to record for the first time the release of endogenous amines -dopamine, serotonin and octopamine- in adult fly brain in vivo, by fast scan cyclic voltammetry. As a proof of principle, we carried out recordings in the calyx region of the Mushroom Bodies, the brain area mainly associated to the generation of olfactory memories in flies. By using principal component regression in normalized training sets for in vivo recordings, we detect an increase in octopamine and serotonin levels in response to electric shock and olfactory cues respectively. This new approach allows the study of dynamic changes in amine neurotransmission that underlie complex behaviors in Drosophila and shed new light on the contribution of these amines to olfactory processing in this animal model.

Comparing risk environments for HIV among people who inject drugs from three cities in Northern Mexico.

BACKGROUND: A large body of research has investigated the rise of injection drug use and HIV transmission in Tijuana and Ciudad Juarez (CJ). However, little is known about the dynamics of injecting in Hermosillo. This study compares drug-related behaviors and risk environment for HIV of people who inject drugs (PWID) across Tijuana, CJ, and Hermosillo to identify factors that could explain differences in HIV prevalence. METHODS: Data from Tijuana belong to a prospective study (El Cuete IV). Data from Hermosillo and Ciudad Juarez belong to a cross-sectional study. Both studies collected data in places where PWID spend time. All participants completed quantitative behavioral and serological testing for HIV. Datasets were merged using only comparable variables. Descriptive statistics tests were used to compare sociodemographic and behavioral characteristics of people who inject drugs PWID sampled in each city. A logistic regression model was built to identify factors independently associated with the likelihood of reporting receptive syringe sharing in the past 6 months. RESULTS: A total of 1494 PWID provided data between March 2011 and May 2012. HIV prevalence differed significantly between participants in Tijuana (4.2%), CJ (7.7%), and Hermosillo (5.2%; p < 0.05). PWID from Hermosillo reported better living conditions, less frequency of drug injection, and lower prevalence of syringe sharing (p < 0.01). PWID from CJ reported a higher prevalence of syringe sharing and confiscation by police (p < 0.01). In a multivariable logistic regression model, living in Hermosillo compared to Tijuana (adjusted odds ratio [AOR] = 0.42, 95% confidence interval [CI] 0.29-0.61) and being female (AOR = 0.61, 95% CI 0.45-0.83) were protective against syringe sharing. Having used crystal meth (AOR = 1.62, 95% CI 1.24-2.13, p = 0.001), having experienced syringe confiscation by police in the last 6 months (AOR = 1.78, 95% CI 1.34-2.40), and lower perception of syringe availability (AOR = 2.15, 95% CI 1.59-2.91) were significantly associated with syringe sharing (p < 0.05). CONCLUSIONS: Differences in HIV prevalence across cities reflect mainly differences in risk environments experienced by PWID, shaped by police practices, access to injection equipment, and dynamics of drug markets. Findings highlight the importance of ensuring sterile syringe availability through harm reduction services and a human rights approach to drug harms in northern Mexico and to generate better understanding of local dynamics and contexts of drug use for designing proper harm reduction programs.

Mechanisms of Kappa Opioid Receptor Potentiation of Dopamine D2 Receptor Function in Quinpirole-Induced Locomotor Sensitization in Rats.

Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of quinpirole, a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist. The mechanism underlying kappa opioid receptor potentiation of quinpirole-induced locomotor sensitization remains to be elucidated. Methods: Immunofluorescence anatomical studies were undertaken in mice brain slices and rat presynaptic synaptosomes to reveal kappa opioid receptor and D2R pre- and postsynaptic colocalization in the nucleus accumbens. Tonic and phasic dopamine release in the nucleus accumbens of rats repeatedly treated with U69593 and quinpirole was assessed by microdialysis and fast scan cyclic voltammetry. Results: Anatomical data show that kappa opioid receptor and D2R colocalize postsynaptically in medium spiny neurons of the nucleus accumbens and the highest presynaptic colocalization occurs on the same dopamine terminals. Significantly reduced dopamine levels were observed in quinpirole, and U69593-quinpirole treated rats, explaining sensitization of D2R. Presynaptic inhibition induced by kappa opioid receptor and D2R of electrically evoked dopamine release was faster in U69593-quinpirole compared with quinpirole-repeatedly treated rats. Conclusions: Pre- and postsynaptic colocalization of kappa opioid receptor and D2R supports a role for kappa opioid receptor potentiating both the D2R inhibitory autoreceptor function and the inhibitory action of D2R on efferent medium spiny neurons. Kappa opioid receptor co-activation accelerates D2R sensitization by contributing to decrease dopamine release in the nucleus accumbens.

Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function.

Dopamine from the ventral tegmental area and glutamate from several brain nuclei converge in the nucleus accumbens (NAc) to drive motivated behaviors. Repeated activation of D2 receptors with quinpirole (QNP) induces locomotor sensitization and compulsive behaviors, but the mechanisms are unknown. In this study, in vivo microdialysis and fast scan cyclic voltammetry in adult anesthetized rats were used to investigate the effect of repeated QNP on dopamine and glutamate neurotransmission within the NAc. Following eight injections of QNP, a significant decrease in phasic and tonic dopamine release was observed in rats that displayed locomotor sensitization. Either a systemic injection or the infusion of QNP into the NAc decreased dopamine release, and the extent of this effect was similar in QNP-sensitized and control rats, indicating that inhibitory D2 autoreceptor function is maintained despite repeated activation of D2 receptors and decreased dopamine extracellular levels. Basal extracellular levels of glutamate in the NAc were also significantly lower in QNP-treated rats than in controls. Moreover, the increase in NAc glutamate release induced by direct stimulation of medial prefrontal cortex was significantly lower in QNP-sensitized rats. Together, these results indicate that repeated activation of D2 receptors disconnects NAc from medial prefrontal cortex and ventral tegmental area. Repeated administration of the dopamine D2 receptor agonist quinpirole (QNP) induces locomotor sensitization. We found that the NAc of QNP-sensitized rats has reduced glutamate levels coming from prefrontal cortex together with a decreased phasic and tonic dopamine neurotransmission but a conserved presynaptic D2 receptor function. We suggest that locomotor sensitization is because of increased affinity state of D2 post-synaptic receptors.

Trends in drug overdose deaths in Mexico (1999-2019). A national descriptive analysis and interstate comparison.

BACKGROUND: We assess trends in overdose mortality rates in Mexico from 1999 to 2019 and identify the states with the highest overdose mortality rates over time. METHODS: The analysis using mortality statistics examined deaths related to drug use. We estimated general overdose mortality rates at the national and state levels and calculated specific mortality rates associated with opioid and stimulant use using central rate estimation. We used joinpoint regression to analyse national and state-specific trends in overdose mortality from 1999 to 2019. FINDINGS: Nationally, the general overdose mortality rate increased annually by 10.49 % (p < 0.01, CI=11.4-18.9) from 2015 to 2019. The northern states of Baja California and Chihuahua were the states with the higher annual increases (18.6 %, p < 0.01, CI=4.2-29.6; and 15.6 %, p < 0.01, CI=12.9-19.7, respectively). By substance type, the national opioid-related mortality rate increased by 29.82 % per year from 2014 to 2019 (p < 0.01; CI=20.1-40.3), compared with an annual decrease of 11.43 % in the previous period (2005-2014) (p < 0.01; CI=-14.7- 8.0). Baja California was the state with the highest rise in opioid-related mortality from 2013 to 2019, with an annual increase of 15.84 % (p < 0.01; CI=1.4-32.3). Stimulant-related mortality increased by 21.79 % per year since 2013 (p < 0.01; CI=16.9-26.9), but it was not possible to calculate state-level trends. CONCLUSIONS: Drug-related mortality rates have increased in Mexico since 2015, particularly in the northern states of Baja California, Chihuahua, Sonora and Sinaloa. Improving harm reduction programmes and local surveillance of fatal and non-fatal overdoses is essential to address the silent escalation of overdose mortality.

Immunolocalization of kappa opioid receptors in the axon initial segment of a group of embryonic mesencephalic dopamine neurons.

The dopamine mesolimbic system is a major circuit involved in controlling goal-directed behaviors. Dopamine D2 receptors (D2R) and kappa opioid receptors (KOR) are abundant Gi protein-coupled receptors in the mesolimbic system. D2R and KOR share several functions in dopamine mesencephalic neurons, such as regulation of dopamine release and uptake, and firing of dopamine neurons. In addition, KOR and D2R modulate each other functioning. This evidence indicates that both receptors functionally interact, however, their colocalization in the mesostriatal system has not been addressed. Immunofluorescent assays were performed in cultured dopamine neurons and adult mice's brain tissue to answer this question. We observed that KOR and D2R are present in similar density in dendrites and soma of cultured dopamine neurons, but in a segregated manner. Interestingly, KOR immunolabelling was observed in the first part of the axon, colocalizing with Ankyrin in 20% of cultured dopamine neurons, indicative that KOR is present in the axon initial segment (AIS) of a group of dopaminergic neurons. In the adult brain, KOR and D2R are also segregated in striatal tissue. While the KOR label is in fiber tracts such as the striatal streaks, corpus callosum, and anterior commissure, D2R is located mainly within the striatum and nucleus accumbens, surrounding fiber tracts. D2R is also localized in some fibers that are mostly different from those positives for KOR. In conclusion, KOR and D2R are present in the soma and dendrites of mesencephalic dopaminergic neurons, but KOR is also found in the AIS of a subpopulation of these neurons.

Long-Range GABAergic Projections of Cortical Origin in Brain Function.

The study of long-range GABAergic projections has traditionally been focused on those with subcortical origin. In the last few years, cortical GABAergic neurons have been shown to not only mediate local inhibition, but also extend long-range axons to remote cortical and subcortical areas. In this review, we delineate the different types of long-range GABAergic neurons (LRGNs) that have been reported to arise from the hippocampus and neocortex, paying attention to the anatomical and functional circuits they form to understand their role in behavior. Although cortical LRGNs are similar to their interneuron and subcortical counterparts, they comprise distinct populations that show specific patterns of cortico-cortical and cortico-fugal connectivity. Functionally, cortical LRGNs likely induce timed disinhibition in target regions to synchronize network activity. Thus, LRGNs are emerging as a new element of cortical output, acting in concert with long-range excitatory projections to shape brain function in health and disease.

Altered Grooming Syntax and Amphetamine-Induced Dopamine Release in EAAT3 Overexpressing Mice.

The excitatory amino acid transporter EAAT3 plays an important role in the neuronal uptake of glutamate regulating the activation of glutamate receptors. Polymorphisms in the gene-encoding EAAT3 have been associated with obsessive-compulsive disorder (OCD), although the mechanisms underlying this relationship are still unknown. We recently reported that mice with increased EAAT3 expression in forebrain neurons (EAAT3 g lo /CMKII) display behavioral and synaptic features relevant to OCD, including increased grooming, higher anxiety-like behavior and altered cortico-striatal synaptic function. The dopamine neurotransmitter system is implicated in ritualistic behaviors. Indeed, dopaminergic neurons express EAAT3, and mice lacking EAAT3 exhibit decreased dopamine release and decreased expression of the dopamine D1 receptor. Moreover, EAAT3 plays a role on the effect of the psychostimulant amphetamine. As such, we sought to determine if the OCD-like behavior in EAAT3 g lo /CMKII mice is accompanied by altered nigro-striatal dopaminergic transmission. The aim of this study was to analyze dopamine transmission both in basal conditions and after an acute challenge of amphetamine, using behavioral, neurochemical, molecular, and cellular approaches. We found that in basal conditions, EAAT3 g lo /CMKII mice performed more grooming events and that they remained in phase 1 of the grooming chain syntax compared with control littermates. Administration of amphetamine increased the number of grooming events in control mice, while EAAT3 g lo /CMKII mice remain unaffected. Interestingly, the grooming syntax of amphetamine-control mice resembled that of EAAT3 g lo /CMKII mice in basal conditions. Using in vivo microdialysis, we found decreased basal dopamine levels in EAAT3 g lo /CMKII compared with control mice. Unexpectedly, we found that after acute amphetamine, EAAT3 g lo /CMKII mice had a higher release of dopamine compared with that of control mice, suggesting that EAAT3 overexpression leads to increased dopamine releasability. To determine postsynaptic effect of EAAT3 overexpression over dopamine transmission, we performed Western blot analysis of dopaminergic proteins and found that EAAT3 g lo /CMKII mice have higher expression of D2 receptors, suggesting a higher inhibition of the indirect striatal pathway. Together, the data indicate that EAAT3 overexpression impacts on dopamine transmission, making dopamine neurons more sensitive to the effect of amphetamine and leading to a disbalance between the direct and indirect striatal pathways that favors the performance of repetitive behaviors.

Age-specific rates of onset of cannabis use in Mexico.

BACKGROUND: Over the previous two decades, the lifetime prevalence of cannabis use has risen among Mexico's population. AIMS: Estimate the sex- and age-specific rates of onset of cannabis use over time. DESIGN: Five nationally representative cross-sectional surveys, the Mexican National Surveys of Addictions (1998, 2002, 2008, 2012) and the Mexican National Survey on Drugs, Alcohol, and Tobacco Consumption (2016). SETTING: Mexico. PARTICIPANTS: Pooled sample of 141,342 respondents aged between 12 and 65 years of which 43.6%(n = 61,658) are male and 56.4% (n = 79,684) are female. MEASUREMENTS: We estimated the age-specific rates of onset of cannabis as the conditional rate of consuming cannabis for the first time at a specific age. METHODS: Time-to-event flexible-parametric models with spline specifications of the hazard function. Stratified analysis by sex and control for temporal trends by year of data collection or decennial birth cohort. FINDINGS: Age-specific rates of onset of cannabis use per 1,000 individuals increased over time for females and males. Peak rates of onset of cannabis use per 1,000 ranged from 0.935 (95%CI = [0.772, 1.148]) in 1998, to 5.391 (95%CI = [4.924, 5.971]) in 2016 for females; and from 7.513 (95%CI = [6.732, 10.063]) in 1998, to 26.107 (95%CI = [25.918,30.654]) in 2016 for males. Across decennial birth-cohorts, peak rates of onset of cannabis use per 1,000 individuals for females ranged from 0.234 (95%CI = [0.078, 0.768]) for those born in the 1930s, to 14.611 (95%CI = [13.243, 16.102]) for those born in the 1990s; and for males, from 4.086 (95%CI = [4.022, 7.857]) for those born in the 1930s, to 38.693 (95%CI = [24.847, 48.670]) for those born in the 1990s. CONCLUSION: Rates of onset of cannabis increased over the previous two decades for both females and males but remained higher for males. Across recent cohorts, the rates of onset have increased at a faster rate among females than males.

Crosstalk Between Kappa Opioid and Dopamine Systems in Compulsive Behaviors.

The strength of goal-oriented behaviors is regulated by midbrain dopamine neurons. Dysfunctions of dopaminergic circuits are observed in drug addiction and obsessive-compulsive disorder. Compulsive behavior is a feature that both disorders share, which is associated to a heightened dopamine neurotransmission. The activity of midbrain dopamine neurons is principally regulated by the homeostatic action of dopamine through D2 receptors (D2R) that decrease the firing of neurons as well as dopamine synthesis and release. Dopamine transmission is also regulated by heterologous neurotransmitter systems such as the kappa opioid system, among others. Much of our current knowledge of the kappa opioid system and its influence on dopamine transmission comes from preclinical animal models of brain diseases. In 1988, using cerebral microdialysis, it was shown that the acute activation of the Kappa Opioid Receptors (KOR) decreases synaptic levels of dopamine in the striatum. This inhibitory effect of KOR opposes to the facilitating influence of drugs of abuse on dopamine release, leading to the proposition of the use of KOR agonists as pharmacological therapy for compulsive drug intake. Surprisingly, 30 years later, KOR antagonists are instead proposed to treat drug addiction. What may have happened during these years that generated this drastic change of paradigm? The collected evidence suggested that the effect of KOR on synaptic dopamine levels is complex, depending on the frequency of KOR activation and timing with other incoming stimuli to dopamine neurons, as well as sex and species differences. Conversely to its acute effect, chronic KOR activation seems to facilitate dopamine neurotransmission and dopamine-mediated behaviors. The opposing actions exerted by acute versus chronic KOR activation have been associated with an initial aversive and a delayed rewarding effect, during the exposure to drugs of abuse. Compulsive behaviors induced by repeated activation of D2R are also potentiated by the sustained co-activation of KOR, which correlates with decreased synaptic levels of dopamine and sensitized D2R. Thus, the time-dependent activation of KOR impacts directly on dopamine levels affecting the tuning of motivated behaviors. This review analyzes the contribution of the kappa opioid system to the dopaminergic correlates of compulsive behaviors.

The Neuronal Glutamate Transporter EAAT3 in Obsessive-Compulsive Disorder.

Obsessive compulsive disorder (OCD) is a heterogeneous psychiatric disorder affecting 1%-3% of the population worldwide. About half of OCD afflicted individuals do not respond to currently available pharmacotherapy, which is mainly based on serotonin reuptake inhibition. Therefore, there is a critical need to search novel and improved therapeutic targets to treat this devastating disorder. In recent years, accumulating evidence has supported the glutamatergic hypothesis of OCD, and particularly pointing a potential role for the neuronal glutamate transporter EAAT3. This mini-review summarizes recent findings regarding the neurobiological basis of OCD, with an emphasis on the glutamatergic neurotransmission and EAAT3 as a key player in OCD etiology.

Correction: Behavioral and synaptic alterations relevant to obsessivecompulsive disorder in mice with increased EAAT3 expression.

The original version of this Article contained an error in the spelling of the author Anna K Radke, which was incorrectly given as Anna R Radke. This has now been corrected in both the PDF and HTML versions of the Article.

Behavioral and synaptic alterations relevant to obsessive-compulsive disorder in mice with increased EAAT3 expression.

Obsessive-compulsive disorder (OCD) is a severe, chronic neuropsychiatric disorder with a strong genetic component. The SLC1A1 gene encoding the neuronal glutamate transporter EAAT3 has been proposed as a candidate gene for this disorder. Gene variants affecting SLC1A1 expression in human brain tissue have been associated with OCD. Several mouse models fully or partially lacking EAAT3 have shown no alterations in baseline anxiety-like or repetitive behaviors. We generated a transgenic mouse model (EAAT3glo) to achieve conditional, Cre-dependent EAAT3 overexpression and evaluated the overall impact of increased EAAT3 expression at behavioral and synaptic levels. Mice with EAAT3 overexpression driven by CaMKIIα-promoter (EAAT3glo/CMKII) displayed increased anxiety-like and repetitive behaviors that were both restored by chronic, but not acute, treatment with fluoxetine or clomipramine. EAAT3glo/CMKII mice also displayed greater spontaneous recovery of conditioned fear. Electrophysiological and biochemical analyses at corticostriatal synapses of EAAT3glo/CMKII mice revealed changes in NMDA receptor subunit composition and altered NMDA-dependent synaptic plasticity. By recapitulating relevant behavioral, neurophysiological, and psychopharmacological aspects, our results provide support for the glutamatergic hypothesis of OCD, particularly for the increased EAAT3 function, and provide a valuable animal model that may open novel therapeutic approaches to treat this devastating disorder.

Genome Sequence of Hydrogenovibrio sp. Strain SC-1, a Chemolithoautotrophic Sulfur and Iron Oxidizer.

Hydrogenovibrio sp. strain SC-1 was isolated from pyrrhotite incubated in situ in the marine surface sediment of Catalina Island, CA. Strain SC-1 has demonstrated autotrophic growth through the oxidation of thiosulfate and iron. Here, we present the 2.45-Mb genome sequence of SC-1, which contains 2,262 protein-coding genes.

Transition from first illegal drug use to first injection among people who inject drugs in Northern Mexico: A retrospective survival analysis / Transición del primer consumo de drogas ilegales a la primera inyección entre las personas que se inyectan drogas en el norte de México: un análisis retrospectivo de supervivencia

Abstract Introduction There is little information in Mexico about the transition to injecting drugs among drug users in cities other than Tijuana. Objective We compare characteristics of the onset of drug use and first injection among people who inject drugs (PWID) from Ciudad Juárez and Hermosillo, two cities of Northern Mexico and identify factors associated with faster rates of transition from first drug use to the first injection. Method 841 PWID were interviewed in 2012 in Ciudad Juárez (n = 445) and Hermosillo (n = 396). Using lifetables, we describe timing at the onset of drug use and first injection. Cox regression analysis was used to determine factors associated with the transition hazard to first injection. Results Median age at onset of drug use was 15.5 years old (standard deviation [SD] = 5.73). The median age at first injection was 21.30 (SD = 7.22). The median duration-time between first drug use and transition to injection was 4.8 years (SD = 5.6). Controlling for sociodemographics, factors that increase the hazard of transitioning to injection are age at onset of drug use (adjusted-hazard-rate [AHR] = 1.04, 95% confidence-interval CI [1.03, 1.05], p<.01) having used cocaine, heroin, or methamphetamine at the onset of drug use (AHR = 1.14, 95% CI [1.03, 1.27], p = .01), and having received assistance at first injection (AHR = 1.25, 95% CI [1.17, 1.33], p<.01). Discussion and conclusion Results show the need to enhance harm reduction programs among non-injecting drug users so as to prevent the spread of injecting drugs in Mexico.

Resumen Introducción Existe poca información en México sobre los calendarios al uso inyectado de drogas en ciudades distintas a Tijuana. Objetivo Comparamos las características del inicio del consumo de drogas y la primera inyección entre las personas que se inyectan drogas (PID) de Hermosillo y Ciudad Juárez e identificamos factores asociados con la transición a la primera inyección. Método En 2012 encuestamos a 841 PID en Ciudad Juárez (n = 445) y Hermosillo (n = 396). Utilizando tablas de vida analizamos las edades al primer uso de sustancias ilícitas y de la primera inyección. Ajustamos un modelo de regresión Cox para determinar los factores asociados con el riesgo de transición a la primera inyección. Resultados La edad mediana al primer consumo de drogas fue 15.5 años (desviación estándar [DE] = 5.73). La edad mediana a la primera inyección fue 21.30 (DE = 7.22). La duración mediana entre el primer uso de drogas ilícitas y la primera inyección fue de 4.8 años (DE = 5.6). Controlando los factores sociodemográficos, los factores que aumentan el riesgo de transición a la inyección son la edad al inicio de uso de drogas ([AHR] = 1.04, intervalo de confianza [IC] del 95% [1.03, 1.05], p<.01) uso de cocaína, heroína o metanfetamina como droga de inicio (AHR = 1.14, IC 95% [1.03, 1.27], p = .01) y haber recibido asistencia en la primera inyección (AHR = 1.25, IC 95% [1.17, 1.33], p<.01). Discusión y conclusión Es necesario mejorar los programas de reducción de daños entre los consumidores de drogas no inyectables para prevenir la propagación del uso inyectado de sustancias en el norte de México.