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La peur influence nos comportements individuels et collectifs qui en retour propulsent l’histoire humaine. Après un aperçu de quelques indices laissant entrevoir le rôle probable de la peur dans l’émergence de la cité, nous examinerons en détail l’expérience de la peur. Puis nous aborderons son impact sur la mémoire, sur le développement du cerveau de l’enfant. Nous verrons ensuite jusqu’à quel point les structures mentales de la peur sont reproduites dans nos systèmes de droits et de devoirs, pour conclure que la sauvegarde de nos démocraties passe par l’apprivoisement et la remémoration de la peur., Fear motivates individual and collective behaviors, which in turn drive human history. After an overview of a few indicators affording us a glimpse into the likely role of fear in the appearance of the city, we shall examine the fear experience in detail. Next we will embark upon its impact on memory and the development of children’s brains. We will then see up to what point mental structures of fear are reproduced in our systems of rights and duties, concluding that the safeguard of our democracies goes through taming and recalling fear.

The psycholinguistic analysis of client– counselor interactions indicates that how individuals talk about their substance use is associated with treatment outcome. However, the processes by which client speech influences out-of-session behaviors have not been clearly delineated. This study investigated the relationships between deriving relations–a key behavioral process by which language and cognition may come to influence behavior, shifts in the strength of client talk in favor of change, and treatment outcome among 75 cocaine-dependent participants (23% Female). Participants were trained to relate cocaine words, nonsense syllables, and negative-consequence words and were then assessed for a derived relation of equivalence before starting treatment. The DARN-C coding system was used to quantify the strength of participant speech during an early cognitive behavior therapy counseling session. Cocaine use during treatment was the outcome of interest. The analyses (a) characterized the process of deriving relations among individuals seeking help for their misuse of cocaine, (b) tested the relationships between shifts in the strength of participants’ speech in favor of change and treatment outcome, and (c) tested if deriving equivalence relations moderated the relationship between shifts in the strength of in-session speech and treatment response. Results indicated that a minority of participants derived equivalence relations, however increases in the strength of commitment language predicted less cocaine use during treatment only among those who did. The findings suggest deriving relations may be an important process by which changes in the strength of commitment language comes to influence substance use.

Background and Objective Hypothesizing that stress dysregulation may worsen cocaine dependence, we investigated the effect of diurnal cortisol secretion profile, suppression of cortisol secretion, and total cortisol secretion on retention, abstinence-based voucher earnings, days of cravings, and mood status of participants at the end of a 2-week medication-free lead-in prior to randomization in a clinical trial of mirtazapine (60 mg vs. placebo) for depressed cocaine-dependent patients. Methods We measured saliva cortisol levels at 9 AM, 2 PM, and 5 PM on the first two consecutive days of a 2-week medication-free lead-in period. Results from saliva samples were used to estimate the total daily level of cortisol, the diurnal profile of secretion (typical vs. atypical), and response to dexamethasone suppression (.1 mg). Seventy-seven patients collected saliva samples at baseline, and 65 (85%) were suitable for profile analysis. Results Patients with typical profiles (52%) collected significantly more abstinence-based voucher earnings during the lead-in (U = 299.50, p = .025). Diurnal secretion profile did not significantly affect mood status, days of craving, or retention. There were no significant effects of suppression of cortisol secretion or of total cortisol levels on any outcome measures. Conclusion In a subgroup of cocaine-dependent patients, deviation of cortisol secretion away from the homeostatic diurnal pattern was associated with reduced success at achieving early abstinence, an important determinant of treatment success. (Am J Addict 2014;23:1–6)

Division on Substance Abuse, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons,Columbia University, New York, New YorkObjective: This study tested the hypothesis that the antidepressantvenlafaxine would be an effective treatment for cocaine abusers withconcurrent depressive disorders.Methods: This was a randomized, 12‐week, double‐blind, placebo‐controlled trial of outpatients (N ¼ 130) meeting DSM‐IIIR criteriaforcocainedependenceandmajordepressionordysthymia(bySCIDinterview). Participants were treated with venlafaxine, up to 300 mg/day versus placebo. All patients received weekly individual manual‐guided relapse prevention therapy. Weekly outcome measuresincluded Clinical Global Impression Scale (CGI), self‐reportedcocaine use, urine toxicology and the Hamilton Depression Scale(Ham‐D).Results: Mood response, defined as a 50% reduction in the Ham‐Dbetween randomization and end of study, was 41% (26/64) onvenlafaxine, and 33% (22/66) on placebo (p ¼ .39). Measures ofdepression (Ham‐D and CGI) improved more rapidly on venlafaxinethan placebo, but these differences disappeared by weeks 6–8.Cocaine outcomes did not differ between treatment groups, and theproportion of patients achieving three or more consecutive weeks ofurine‐confirmed abstinence was low (venlafaxine: 16%; placebo:15%). Reduction in cocaine use was associated with mood response.Conclusions: Overall, venlafaxine was not superior to placebo oneither mood or cocaine use outcomes. Mood improvement wasassociatedwithimprovementincocaineuse.However,placebomoodresponse was only moderate, and the proportion of patients achievingsustained abstinence was low. This suggests that the subgroup ofcocaine‐dependent patients with depressive disorders is relativelytreatment resistant, and that further research is needed to improveoutcomes for these patients. (Am J Addict 2014;23:68–75)

Understanding the form of clinical change can help guide the development of more effective treatment strategies for opiate dependence. This study investigated the process of change by modeling transitions among four clinical states encountered among 64 detoxified opiate-dependent individuals treated with daily oral naltrexone: no opiate use, blocked opiate use (i.e. opiate use while adhering to oral naltrexone), unblocked opiate use (i.e. opiate use after having discontinued oral naltrexone), and treatment drop-out. The effects of baseline characteristics and two psychosocial interventions of differing intensity, Behavioral Naltrexone Therapy (BNT) and Compliance Enhancement (CE), on these transitions were investigated. Heavier opiate users were more likely to be retained in a comprehensive psychosocial intervention (i.e. BNT). Markov modeling indicated a transition from abstinence to the discontinuation of treatment was approximately 3.56 times greater among participants in CE relative to BNT indicating the more comprehensive psychosocial intervention kept participants engaged in treatment longer. Transitions to stopping treatment were more likely to occur following unblocked opiate use in both treatments. Continued opiate use while being blocked (i.e. extinction) accounted for a relatively low proportion of transitions to abstinence and may have more deleterious effects later in the treatment episode.

Co-occurring psychiatric disorders have been associated with poor prognosis among substance-dependent patients, but few studies have examined this association among patients with cocaine dependence (CD). We compared baseline characteristics and treatment outcome between cocaine-dependent patients with major depressive disorder (MDD; n = 66), those with attention-deficit/hyperactivity disorder (ADHD; n = 53), and those with CD without comorbid disorders (CD alone; n = 48) who had been randomized to the placebo arms of clinical trials with venlafaxine, methylphenidate, and gabapentin, respectively. The three groups differed significantly in racial makeup, with more Caucasians and Hispanics among patients with MDD and those with ADHD but more African Americans among those with CD alone. The groups did not differ significantly in treatment retention, with retention rates ranging from 42% to 47%; neither did they differ in the rates of achieving 2 consecutive weeks of urinalysis-confirmed abstinence, with rates ranging from 40% to 50%. Using logistic regression for repeated measures with general estimating equations, modeling the likelihood of a cocaine-positive week over time in treatment, we found the diagnostic group to interact with the baseline level of cocaine use and time. Among cocaine-dependent patients who achieved abstinence at baseline, those with MDD and those with ADHD had better outcome over time as compared with patients with CD alone. However, among patients with cocaine-positive urine specimens at baseline, those with MDD and those with ADHD were associated with poor outcome as compared with patients with CD alone. The findings suggest that diagnosis and treatment of co-occurring disorders such as depression and ADHD may be important components of treatment planning for CD and that the baseline level of cocaine use should be included as a covariate in studies evaluating the impact of such treatment.

Antisocial personality disorder (ASPD) is highly associated with substance use disorders (SUD). In addition to the full ASPD syndrome, which requires both childhood conduct disorder and the adult features, other antisocial behavioral syndromes, including conduct disorder (CD) alone without the adult syndrome, and the adult antisocial behavioral syndrome without childhood CD (AABS) are also frequently diagnosed in patients with SUD. The aim of this study was to compare the rates of these various ASPD syndromes between cocaine- and cannabis-dependent individuals seeking treatment. A structured interview for ASPD excluding symptoms that occurred solely in the context of substance use was conducted in 241 outpatients (cocaine dependence, n = 111; cannabis dependence, n = 130). Overall, the proportion of substance-dependent individuals in this study with AABS was significantly larger than the proportion with ASPD (30.9% vs. 17.3%). A diagnosis of CD-only, where CD did not progress to ASPD, was uncommon. No significant differences in the prevalence of antisocial behavioral syndrome diagnoses were found between cocaine- and cannabis-dependent patients. Antisocial behavioral syndrome diagnosis did not influence treatment retention. Antisocial behavioral syndromes are commonly diagnosed in patients with SUD and future research should evaluate prognostic implications of AABS compared to ASPD in a variety of clinical treatment settings.

During a randomized, double-blind, placebo controlled study of the effects of sertraline in depressed methadone-maintained patients, 82 completed the tridimensional personality questionnaire (TPQ) to assess whether temperament dimensions can affect treatment-related changes in mood and drug use. Mood outcome significantly differed according to scores on the reward dependence scale (RD). Low RD participants displayed a significantly better mood response to sertraline than high RD participants. Participants with high harm avoidance (HA) scores were more likely to be abstinent at the end of the 12 week trial of sertraline than low HA participants. High persistence (P) participants were less likely to be abstinent at the end of the 12-week trial. These results suggest that temperament dimensions may be important for identifying substance dependent patients more likely to benefit from pharmacological interventions for comorbid depressive disorders.

We examined whether drug use behaviors during a 2-week lead-in for a pharmacotherapy trial were predictive of retention in treatment and of the level of cocaine use during the subsequent 12 weeks of treatment. Fifty cocaine dependent patients were grouped based on: (1) principal route of cocaine administration: intranasal versus smoking, and (2) level of cocaine use during the 2-week lead-in: high versus low. Results indicate that level of cocaine use during the 2-week lead-in was a significant predictor of cocaine use during the subsequent 12 weeks of treatment. Patients with reported higher level of use during the lead-in period were more likely to continue using cocaine during the treatment. Patients who used smoking as their primary route of cocaine use were more likely to drop out early in the treatment. Findings of this study suggest that route and level of cocaine use during lead-in be used as a covariate in models testing treatment effect.

Background Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). Methods Opioid dependent participants were randomized to receive dronabinol 30 mg/d ( n = 40) or placebo ( n = 20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. Results The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group ( p = 0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Conclusion Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.

There is an accumulating body of research suggesting that suicidal behavior may be associated with abnormalities of the central serotonin system. Other monoaminergic, peptidergic, and neuroendocrine systems have been implicated as well. A review of studies that examine neurobiological variables in postmortem tissue of suicide victims and controls reveals that investigators in most instances have viewed age as a confound to be controlled rather than considering it as a variable of interest. However, the close associations between aging and increased suicide rates, and the knowledge that the functional integrity of many of these same systems changes with normal and abnormal aging processes, raise the possibility that biological aging contributes to suicide risk, and that the underlying neurobiology of suicide in the elderly differs from that of younger people. The few available studies that did examine the association of age with neurobiological measures indicate directions for future research into the role that aging may play in determining the biological bases of suicide risk.

Background Preclinical findings suggest that the inhibition of NMDA glutamatergic neurotransmission may have beneficial effects in the treatment of opioid dependence. Aims We hypothesized that memantine, a low-potency, uncompetitive NMDA receptor antagonist, would be safe and effective when used as an adjunct to oral naltrexone in the treatment of opioid dependence, particularly in preventing relapse to opiate use in detoxified individuals. Methods Opioid-dependent participants (N = 112) were enrolled. Following detoxification all participants were inducted onto oral naltrexone and were randomized to receive memantine 15 mg bid (N = 27), memantine 30 mg bid (N = 27) or placebo (N = 27) for 12-weeks in combination with naltrexone 50 mg/day and individual relapse-prevention therapy. The primary outcome was the retention in treatment since treatment dropout is most commonly associated with relapse to opiate use. Results Twenty-six percent of participants withdrew from treatment prior to starting naltrexone. Of those that were randomized 35% completed 4 weeks only, and 24% completed all 12 weeks of treatment. There was no significant difference in treatment retention or heroin use, opiate withdrawal symptoms and craving between the groups treated with memantine vs. placebo. Conclusion Thus, the efficacy of memantine 30 or 60 mg/day as an adjunct to oral naltrexone for the treatment of opiate dependence was not supported.

Preclinical findings suggest that the inhibition of NMDA glutamatergic neurotransmission may have beneficial effects in the treatment of cocaine dependence. We hypothesized that memantine, a low potency, uncompetitive NMDA receptor antagonist, would be safe and effective in the treatment of cocaine dependence, particularly in preventing relapse to cocaine use in abstinent individuals. Cocaine dependent patients ( N = 112) were enrolled. The trial began with a 2-week placebo lead-in period during which patients received high-value voucher contingency management to induce abstinence. Participants were then randomized to receive either memantine 20 mg bid ( N = 39) or placebo ( N = 42) for 12-weeks in combination with individual relapse-prevention therapy. The randomization was stratified by abstinence status during the lead-in period. The primary outcome was the weekly proportion of days of cocaine use. There were no significant differences in cocaine use outcome between the groups treated with memantine versus placebo. Thus, the efficacy of memantine 40 mg/d for the treatment of cocaine dependence was not supported. Urine-confirmed abstinence during the lead-in period was achieved by 44% of participants, and was a strong predictor of subsequent cocaine abstinence during the trial. This suggests that this clinical trial design, an intensive behavioral intervention during a lead-in period, resolves cocaine dependent patients into two subgroups, one that rapidly achieves sustained abstinence and may not need a medication, and another that displays persistent cocaine use and would most likely benefit from a medication to help induce abstinence. Targeting the latter subgroup may advance medication development efforts.

Naltrexone is a theoretically promising alternative to agonist substitution treatment for opioid dependence, but its effectiveness has been severely limited by poor adherence. This study examined, in an independent sample, a previously observed association between moderate cannabis use and improved retention in naltrexone treatment. Opioid dependent patients (N = 63), admitted for inpatient detoxification and induction onto oral naltrexone, and randomized into a six-month trial of intensive behavioral therapy (Behavioral Naltrexone Therapy) versus a control behavioral therapy (Compliance Enhancement), were classified into three levels of cannabis use during treatment based on biweekly urine toxicology: abstinent (0% cannabis positive urine samples); intermittent use (1% to 79% cannabis positive samples); and consistent use (80% or greater cannabis positive samples). Intermittent cannabis users showed superior retention in naltrexone treatment (median days retained = 133; mean = 112.8, SE = 17.5), compared to abstinent (median = 35; mean = 47.3, SE = 9.2) or consistent users (median = 35; mean = 68.3, SE = 14.1) (log rank = 12.2, df = 2, p = .002). The effect remained significant in a Cox model after adjustment for baseline level of heroin use and during treatment level of cocaine use. Intermittent cannabis use was also associated with greater adherence to naltrexone pill-taking. Treatment interacted with cannabis use level, such that intensive behavioral therapy appeared to moderate the adverse prognosis in the consistent cannabis use group. The association between moderate cannabis use and improved retention on naltrexone treatment was replicated. Experimental studies are needed to directly test the hypothesis that cannabinoid agonists exert a beneficial pharmacological effect on naltrexone maintenance and to understand the mechanism.

The purpose of this 12-week open trial was to evaluate the potential utility of atomoxetine for the treatment of attention deficit hyperactivity disorder (ADHD) in cocaine-dependent treatment seekers. The sample consisted of 20 participants with all participants meeting DSM-IV-TR criteria for ADHD and cocaine dependence (CD). Using several measures to assess ADHD, there was a significant reduction in ADHD symptoms. There was no significant decrease in cocaine use throughout the trial. Taken together, although cocaine-dependent individuals showed some reduction in ADHD symptoms while receiving atomoxetine, the high drop-out rate and lack of impact on cocaine use may limit its utility in ADHD adults who are currently abusing cocaine.

Opioid dependence is a growing public health problem. Maintenance on the antagonist naltrexone for clinic- or office-based treatment of opioid dependence is plagued by high rates of relapse. This paper identifies critical determinants of lapses to opioid use during naltrexone maintenance. Time retained in treatment was examined as a function of whether lapses to opioid use occurred while adherent to naltrexone (blocked use), or after having missed naltrexone doses (unblocked). Method Participants ( N = 83) met DSM-IV criteria for opioid dependence and identified a significant other willing to participate in their treatment. Following inpatient detoxification, participants were enrolled in a 26-week outpatient course of therapy and naltrexone maintenance. Results Patients with unblocked use had a very high rate of dropout (10% retained at 6 months), dropout usually occurring within 2 weeks after unblocked use. Patients with only blocked use had less dropout (33% retained at 6 months). However, episodes of blocked use were often followed by unblocked use and dropout. Conclusions During naltrexone maintenance for opioid dependence unblocked opioid use calls for immediate intervention, such as detoxification or switching to the partial agonist buprenorphine. Episodes of blocked use warrant increased clinical attention, such as direct observation of naltrexone ingestion, increased dose, or increased intensity of treatment contact. Maintenance on oral naltrexone is a fragile treatment because it is so easily undermined by episodes of opioid use while non-compliant. New long-acting injectable or implantable formulations of naltrexone may address this limitation and should be investigated for treatment of opioid dependence.

Cocaine dependence (CD) is often accompanied by major depressive disorder (MDD). The comorbid condition (CD + MDD) is especially difficult to treat, with relapse possibly made more likely by intensified dysphoria during abstinence in the setting of MDD. We studied treatment-seeking CD + MDD volunteers, currently depressed, and a comparison CD group over three days of inpatient monitored abstinence. At admission, Beck Depression Inventory (BDI) and anxiety scores differed significantly between groups. By Day 3, BDI scores improved for both CD and CD + MDD groups. The mood response to cocaine cessation among CD + MDD individuals resembled that of CD participants, contrary to some expectations.

Cannabis is the most widely used illicit substance in the United States with especially high prevalence of use among those with psychiatric disorders. Few studies have examined the relationship between concurrent cannabis use and treatment outcome among patients receiving treatment for comorbid substance abuse and psychiatric disorders. This study investigated the effects of cannabis use on treatment retention and abstinence from cocaine among cocaine dependent patients with Attention Deficit Hyperactivity Disorder (ADHD). Cocaine dependent patients diagnosed with current ADHD (DSM-IV, N = 92) aged 25 to 51 participated in a randomized clinical trial of methylphenidate for treatment of ADHD and cocaine dependence in an outpatient setting. The majority of patients (69%) used cannabis during treatment. Results suggest that moderate/intermittent cannabis users had greater retention rates compared to abstainers and consistent users (p = .02). This study is the first to examine concurrent cannabis use in cocaine dependent patients diagnosed with ADHD.

Although marijuana dependence is prevalent, most individuals with marijuana dependence do not seek treatment. There are few data characterizing treatment seeking marijuana-dependent patients compared to patients presenting for treatment of other drugs regarding the severity of illness and motivation for treatment. Forty-two marijuana-dependent individuals were compared to 58 cocaine-dependent individuals seeking treatment. Compared to cocaine-dependent patients, those with marijuana dependence were younger and less likely to be dependent on alcohol or other drugs. Both groups had similar rates of comorbid anxiety and affective disorders. Marijuana-dependent individuals had lower total number of dependence symptoms but had a higher percentage of individuals endorsing withdrawal symptoms. Although marijuana-dependent individuals had less outpatient treatment exposure, the difference between the two groups was not significant and motivation for change, based on the University of Rhode Island Change Assessment, was similar for both groups of treatment seekers. However, the Circumstances, Motivation, Readiness for Treatment Scale suggested that cocaine-dependent individuals were more motivated for treatment. Taken together, these data suggest that treatment seeking marijuana-dependent individuals have substantial withdrawal dependence symptomatology although it is less clear if they are as motivated to seek out treatment as cocaine-dependent treatment seekers.

Background In laboratory animals, augmentation of GABA neurotransmission results in inhibition of cocaine self-administration and inhibition of reinstatement to cocaine-seeking behaviors. If parallel effects were observed in humans, GABA-ergic medication should be effective both in the abstinence–induction as well as in the relapse-prevention phase of cocaine dependence treatment. Gabapentin is an anticonvulsant medication that increases human brain GABA levels. We evaluated the safety and efficacy of gabapentin combined with relapse-prevention therapy in the treatment of cocaine-dependent individuals. Design The study involved 129 individuals with cocaine dependence. Of the 99 participants, who were randomized into a double-blind trial 88% were males, 66% were minorities and with an average age of 39 years (range 22–58 years). After 2 weeks of placebo lead-in, participants were randomized to receive either gabapentin 3200 mg (1600 mg bid) or placebo for 12 weeks, followed by 2 weeks of placebo lead-out. Prior to randomization, participants were stratified into four groups based on the principal route of cocaine use (smokers versus intranasal users) and the level of cocaine use during the 2 weeks of lead-in (high level versus low level). Throughout the 16 weeks study, participants received weekly individual relapse-prevention therapy. The outcome measures included: days of cocaine use and a binary indicator of abstinence based on urine toxicology test, self-reported cocaine craving and retention in treatment. Results Forty-nine percent of randomized patients completed 12 weeks of the trial. Retention did not differ by treatment group but cocaine-smokers dropped out of treatment at a significantly faster rate than intranasal users. For the entire sample, odds of cocaine use over the course of the study did not differ between gabapentin- and placebo-treated individuals. There was a significant difference in the odds of cocaine use between high and low-use groups, with the odds in high-use groups decreasing over time and odds in the low-use groups gradually increasing over the course of the study, such that by the end of the study low and high users were similarly likely to use cocaine. In the low-use group, there was a non-significant trend suggesting that gabapentin-treated subjects had more favorable outcome compared to placebo-treated individuals. There was no treatment effect on abstinence rates, craving or other substance use. Gabapentin at 3200 mg/day was very well tolerated in this group of cocaine-dependent participants. Conclusions When combined with weekly individual relapse-prevention therapy, gabapentin 1600 mg bid was no more effective than placebo in the treatment of cocaine dependence. When reviewed in conjunction with other published studies, gabapentin and other GABA enhancing anticonvulsant medications may deserve further study as relapse-preventive agents in cocaine-dependent individuals who achieve abstinence early in treatment.

Publisher Summary There is substantial anatomical documentation of projections to the hypothalamic paraventricular nucleus from the caudal ventrolateral and dorsomedial medulla. Moreover, electrophysiological data do indeed indicate that electrical stimulation in the caudal ventrolateral medulla (cVLM) and the caudal nucleus tractus solitarius (cNTS) is facilitatory to paraventricular vasopressin-secreting magnocellular neurosecretory neurons. Data from supraoptic nucleus, which is composed almost exclusively of magnocellular neurons projecting to the neurohypophysis, also support a selective excitatory input from A1 ventrolateral medulla cells to vasopressin-secreting neurons. In contrast, preliminary observations indicate that electrical stimulation in cNTS excites both vasopressin- and oxytocin-secreting supraoptic neurons. Inputs to the NTS arriving in glossopharyngeal and vagal afferents have at least two pathways whereby they can influence hypothalamic magnocellular neurosecretory neurons. Information destined to enhance the activity of vasopressinergic neurons—for example, through the unloading of peripheral baroreceptors consequent to hemorrhage or the loss of blood volume—seems to be preferentially channeled through the A1 neurons of the caudal ventrolateral medulla.