Psychopathology in substance abusing women reporting childhood sexual abuse.

This study compared MMPI-2 profiles and evaluated the ability of the MMPI-2 and its two new post-traumatic stress scales (PK and PS) to discriminate women in outpatient substance abuse treatment reporting positive (n = 24) and negative (n = 69) child sexual abuse histories. T-tests revealed significantly higher mean scores for the sexual abuse group for the following scales: F, 1, 2, 3, 4, 6, 7, and 8. A discriminant analysis yielded a linear function of L, F, 3, 5, 8, and PK that correctly categorized 75% with positive histories and 77% with negative histories. The optimal cutoff PK score was 17, which correctly classified 75% and 46% of those reporting positive and negative abuse histories, respectively. These findings support early identification of abuse survivors among substance abusing women and suggests that the MMPI-2 may be useful in patient-treatment matching.

The evaluation of a consultation service for delivery of substance abuse services in a hospital setting.

OBJECTIVE: This study evaluated the institutional impact of a substance abuse consultation service in a hospital setting. METHOD: Treatment and matched comparison groups were compared on five outcome variables: length of stay, total cost, reimbursement, readmission, and appropriateness of care. The treatment group consisted of patients with discharge diagnoses falling into targeted Diagnostic Resource Groups (DRGs) and who received a substance abuse consultation. The comparison group consisted of patients with the same targeted DRGs, a coexisting substance abuse diagnosis, and who did not receive a substance abuse consultation. RESULTS: No statistically significant differences were found for the five outcome variables. Findings closely approached statistical significance for rate of readmission with treatment patients being less likely to be readmitted during the 12 months following the consultation. CONCLUSIONS: Although cost savings were not found during the hospitalization when the substance abuse consultation was provided, the data suggests that the consultation may reduce the need for readmission during the year following discharge.

Perinatal substance abusers: factors influencing treatment retention.

This study investigated the association between two demographic and two psychological variables and treatment retention for 65 perinatal substance abusers. Subjects who lived in the community while attending day treatment were 6.125 times more likely to drp out than subjects who lived in a program-operated shelter (p < .0001). An interaction was found for pregnancy status and antisocial personality disorder (p < .0478). Subjects who were both pregnant and antisocial were 4.876 times more likely to remain in treatment than those who were neither pregnant nor antisocial. Degree of "treatment resistance," measured by the MMPI Negative Treatment Indicators (TRT) Scale, did not predict dropout. These findings indicate that supportive housing can play an important role in preventing dropout for perinatal substance abusers. Additionally, pregnancy may present a "window" of opportunity for treating a hard to reach population, drug abusing women with comorbid ASP.

Changes in immunologic cell surface markers during cocaine withdrawal in pregnant women.

To evaluate the effects of acute cocaine withdrawal on the immune system of pregnant women, we analyzed changes in a panel of cell surface markers and plasma proteins that have immunological importance. The cell surface markers included complement receptors [CR1 (CD35), CR2 (CD21), CR3 (CD11b, CD18)], immunoglobulin Fc receptors [FcgammaRII (CD32), FcgammaRIII (CD16)], proteins important for lymphocyte function [CD3, CD4, CD8, CD19, CD25, CD45RA], and the framework antigen HLA-ABC. We also measured levels of the plasma proteins C3, C4, IgG, IgM, and IgA, along with the cytokine interleukin-2, soluble lymphocyte markers sCD25, sCD4, sCD8, IL-2, and soluble immune complexes. While no significant changes were seen in the levels of plasma proteins, changes paralleling the course of acute withdrawal were seen in complement receptors and immunoglobulin Fc receptors on leukocyte subpopulations. By contrast, proteins important for lymphocyte function were relatively unperturbed. There was an increase in receptor expression at the onset of withdrawal that peaked 3-5 days after last cocaine use, followed by a decrease in expression to initial (pre-withdrawal) levels. These changes in cell surface receptors may reflect altered immune function in the women who were withdrawing from cocaine.

Attitude toward recovery and completion of a substance abuse treatment program.

This study tested the ability of the Recovery Attitude and Treatment Evaluator (RAATE; Mee-Lee, Hoffmann, & Smith, 1992) to predict attrition from treatment for pregnant and postpartum substance abusing women. During the first month of treatment, the RAATE was completed by both the clinician and the patient. Three types of discharge status were considered: completion of the treatment program, dropping out of the program, and being administratively discharged. No group differences were found concerning the clinician version of the RAATE. Initial analyses of the patient version revealed that subjects who completed the program had lower ratings of resistance to treatment and continuing care compared to those who dropped out; further analysis suggested that those who completed less than 1 month of treatment exhibited the highest resistance. These results suggest the RAATE is a potentially effective tool for predicting early attrition from substance abuse treatment in this population.

Decreased carbon dioxide sensitivity in infants of substance-abusing mothers.

OBJECTIVE: To determine whether there is a demonstrable abnormality in control of breathing in infants of substance-abusing mothers during the first few days of life. METHODS: We enrolled 12 drug-free control infants and 12 infants of substance abusing mothers (ISAMs). These infants experienced otherwise uncomplicated term pregnancies and deliveries. The infants were assigned to a group based on the results of maternal histories and maternal and infant urine toxicology screens. Studies were performed during quiet sleep during the first few days of life. We measured heart rate, oxygen saturations via a pulse oximeter, end-tidal carbon dioxide (ET-CO2) level, respiratory rate, tidal volume, and airflow. The chemoreceptor response was assessed by measuring minute ventilation and the ET-CO2 level after 5 minutes of breathing either room air or 4% carbon dioxide. RESULTS: The gestational ages by obstetrical dating and examination of the infants were not different, although birth weights and birth lengths were lower in the group of ISAMs. Other demographic data were not different, and there were no differences in the infants' median ages at the time of study or in maternal use of tobacco and alcohol. The two groups had comparable baseline (room air) ET-CO2 levels, respiratory rates, tidal volumes, and minute ventilation. When compared with the group of ISAMs, the drug-free group had markedly increased tidal volume and minute ventilation on exposure to 4% carbon dioxide. These increases accounted for the difference in sensitivity to carbon dioxide, calculated as the change in minute ventilation per unit change in ET-CO2 (milliliters per kg/min per mm Hg). The sensitivity to carbon dioxide of control infants was 48.66 +/- 7.14 (mean +/- SE), whereas that of ISAMs was 16.28 +/- 3.14. CONCLUSIONS: These data suggest that ISAMs are relatively insensitive to challenge by carbon dioxide during the first few days of life. We speculate that this reflects an impairment of the chemoreceptor response.

Drug-using and nonusing women: potential for child abuse, child-rearing attitudes, social support, and affection for expected baby.

Eighty pregnant women (25 substance using, 55 nonusing) from an American prenatal clinic serving lower-income to working-class women responded to questionnaire measures of child-rearing attitudes. The drug users' primary substance of misuse was cocaine (68%), alcohol (16%), amphetamines (12%), or sedatives (4%); polydrug use was documented for 80% of the women. The two (user and nonuser) groups were not different on demographic (age, race, marital status, education, SES, source of income) or obstetrical factors (number of pregnancies, number of children). Drug-using women scored significantly higher on a measure of child abuse potential; more than half scored in the range of clinical criterion for extreme risk. As their babies were not yet born, no actual physical abuse was documented, only a higher potential for abuse. The subgroup who were both drug users and had lower social support scored higher on child abuse potential than all other subgroups. The drug users also had lower self-esteem scores than the nonusers. The two groups did not differ on measures of overall social support, authoritarian/democratic child-rearing beliefs, or affection for the expected baby.

Perinatal substance abusers. Psychological and social characteristics.

Forty perinatal substance abusers were administered multiple psychosocial, addiction, and psychological measures before beginning treatment. Results indicate that these patients are limited intellectually, educationally, financially, and emotionally. Psychiatric comorbidity was high, with 45% having non-substance abuse axis I diagnoses and 75% having confirmed (by two or more tests) axis II pathology. The most frequently identified axis I disorders were depression and anxiety. The most frequently detected personality disorders were antisocial, borderline, paranoid, and dependent. The average IQ was 87 (low average range) and nearly one third of the sample were found to be somewhat impaired intellectually. These data suggest that treatment programs must take psychological characteristics into account if they are going to succeed in helping these women achieve and maintain abstinence.

Social support and anxiety in pregnant drug abusers and nonusers: unexpected findings of few differences.

Drug-abusing (n = 25) and nonusing (n = 55) pregnant women from a publicly supported prenatal clinic were tested for level of social support and of pregnancy anxiety during the last half of pregnancy. Differences found between the groups were fewer than expected. Drug abusers did not differ from nonusers in overall level of social support or in Appraisal, Belonging, or Tangible subscales. Abusers were found to report lower levels of self esteem; lower self esteem was predicted by drug abuse, having more children and lower socioeconomic status. Drug abusers did not differ from nonusers in their overall feelings of pregnancy anxiety, but they did indicate higher fears for themselves and for the baby, and there was a tendency for higher depression and withdrawal.

Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use.

OBJECTIVES: To compare the efficacy of structured questionnaire screening and prenatal urine toxicology for the detection of substance use by pregnant women, and to describe substance use patterns in a group of women presenting to a university-based obstetric clinic. METHODS: All patients presenting to our obstetric clinic for their first prenatal visit were evaluated for evidence of current use of alcohol or any illicit substances. Nursing personnel administered an extensive questionnaire, which included detailed questions about past and current substance use patterns. Urine samples were examined by a commercial laboratory for alcohol and a number of illicit substances. Current users were defined as those who admitted use within the past 30 days or who had positive urine toxicology. RESULTS: Fifty-eight of 302 patients (19.2%) were identified as current users of alcohol or illicit substances. Only 17 of 41 women (41.5%) with toxicologic evidence of recent use admitted to current use. Only 17 of 34 (50.0%) admitting to current use had toxicology positive for any substance. Patients with a history of multiple past substance use were significantly more likely to have positive urine toxicology than those without such a history (26.1 versus 7.4%; P < .005). Among current users, multiple substance use (34.5%) and cigarette smoking (52%) were common. CONCLUSION: A screening combination of structured questionnaire and universal urine toxicology identifies more current users than either technique alone, and neither is clearly superior to the other. A history of multiple substance use may be an important indicator of current use.

Effects of ethanol and toluene on fixed-ratio performance in short sleep and long sleep mice.

This study examined the effects of ethanol (EtOH) and toluene on fixed-ratio (FR) responding in mice selectively bred for sensitivity to the effects of EtOH on sleep time. Although the more sensitive long sleep (LS) mice showed greater EtOH-induced impairment in a motor performance task than did the less sensitive short sleep (SS) mice, changes in FR performance in the two lines did not differ in response to EtOH, regardless of route (oral or intraperitoneal) or time (40 vs. 60 min pre-session) of administration. These results emphasize the importance of considering task variables in determination of the behavior of different genotypes. In contrast to results with EtOH, the volatile inhalant toluene produced different effects on FR responding in the selected lines, with SS mice being more sensitive than LS mice.

Electroencephalographic sleep and mood during cocaine withdrawal.

We report on nine patients between the ages of 21 and 39 years who were admitted to an inpatient substance abuse treatment unit for cocaine treatment. The patients' sleep was studied in the laboratory for 4 nights during the first week, and 2 nights during the second and third weeks of their hospitalization. Daily mood ratings, cocaine craving scores and sleep logs were also recorded on each patient. During the first week of withdrawal, these patients had a markedly shortened REM latency, an increased REM sleep percentage, a very high REM density and a long total sleep period time. During the third week, REM latencies were very short and total percentage of REM sleep was increased. By week three of withdrawal the sleep continuity pattern was similar to that found in chronic insomnia, with a long sleep latency, an abnormally increased total time awake after sleep onset and a poor sleep efficiency. The subjects' ratings of cocaine craving, total POMS scores and depression fell precipitously after the first week of withdrawal and were at sub-clinical levels by week three of withdrawal.

Ethanol-like discriminative stimulus effects of non-competitive n-methyl-d-aspartate antagonists.

The discriminative stimulus effects of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists were investigated in animals trained to discriminate 1.5g/kg (pigeons) or 1.25g/kg (mice) ethanol from vehicle. Key-pecking of pigeons and lever responding of mice were maintained under fixed ratio schedules of mixed grain or milk reinforcement, respectively. Phencyclidine (PCP) and ketamine dose-dependently substituted for the ethanol stimulus in both species, with PCP being about 10-fold more potent than ketamine. In pigeons, PCP and ketamine fully substituted for ethanol at doses that did not significantly alter rates of responding; with mice, complete substitution was accompanied by response rate-decreasing effects. In pigeons, the highly selective NMDA receptor/ionophore antagonist MK-801 also substituted for ethanol at a dose that was accompanied by reduced response rates. Compounds that did not substitute for the ethanol stimulus were cocaine (both species), the 5-HT(1B) receptor agonist TFMPP (pigeon), the H(1) receptor antagonist hydroxyzine (mice), and the anticonconvulsants phenytoin and ethosuximide (mice). The present data show that PCP-like drugs that are antagonists of NMDA receptor-mediated neurotransmission share common discriminative stimulus effects with ethanol.

Adaptation of body temperature and nociception to cold stress in preweanling rats.

In order to investigate the response of rat pups to stress, 10-day-old rats (N = 10) were exposed to cold water (14 degrees C) for 5 min or to a control treatment (N = 10) for 5 consecutive days. On the sixth day when the rats were 15 days of age, all rat pups were immersed in cold water for 5 min. Body temperature and nociceptive threshold were recorded as functional indexes of the stress response to cold water. Results revealed that the rat pups that had been previously exposed to the cold stressor demonstrated a smaller decline in body temperature and a smaller increase in nociceptive threshold following cold-water immersion than rat pups which had no prior experience with the stressor. Thus, as measured by thermoregulatory and nociceptive function, 15-day-old rat pups are capable of adapting to repeated stressful experiences.

Discriminative stimulus properties of toluene in the rat.

Rats were trained to discriminate toluene (100 mg/kg, IP) from vehicle in a two-lever operant task. Acquisition of the discrimination required a range of 85-219 training days. Injections of either methohexital (0.5-10 mg/kg) or oxazepam (0.5-20 mg/kg) produced toluene-lever responding in a dose-dependent fashion in most animals. The discriminative stimulus properties of toluene were not found to generalize to chlorpromazine (0.3-10 mg/kg). These results are consistent with those obtained in the mouse and provide further evidence that toluene has stimulus properties similar to those of CNS depressant drugs. These results further suggest that toluene may have drug abuse potential of the CNS depressant type.

Effects of carbon monoxide in combination with behaviorally active drugs on fixed-ratio performance in the mouse.

The effects of carbon monoxide (3.75, 7.5, 15 and 30 ml/kg, IP) alone and in combination with ethanol (1.1 g/kg), nicotine (1.1 mg/kg), caffeine (36.1 mg/kg), chlorpromazine (2.2 mg/kg), diazepam (10 mg/kg), pentobarbital (23.1 mg/kg), d-amphetamine (1.4 mg/kg) or morphine (13.3 mg/kg) were evaluated in mice. Animals were trained to lever press under a fixed-ratio 32 schedule of water reinforcement. Response rates following CO-drug combinations were compared with the expected additive effects determined by the sum of the effects of each agent administered alone. CO (15 and 30 ml/kg) in combination with ethanol produced supra-additive effects. CO-chlorpromazine and CO-d-amphetamine combinations often produced greater than additive response-rate suppression, although differences from additivity did not reach statistical significance. The effects on response rates following CO in combination with nicotine, caffeine, diazepam, pentobarbital, or morphine were additive. These results suggest that concurrent use of therapeutic or abused drugs and CO exposure may place an individual at higher risk for behavioral toxicity.

Assessment of the abuse potential of acetorphan, an enkephalinase inhibitor.

The discriminative stimulus properties, reinforcing effects and physical dependence potential of acetorphan, a parenterally-active enkephalinase (E.C. 3.4.21.11) inhibitor, were assessed in the present studies. Rats trained to discriminate 2 mg/kg morphine from saline did not generalize to acetorphan at any dose tested (5-50 mg/kg). Acetorphan also had minimal reinforcing effects in rhesus monkeys. When acetorphan was substituted for cocaine, one dose (300 micrograms/kg per inj.) maintained responding somewhat above the range of vehicle values in only two of the four monkeys tested. In physical dependence studies, acetorphan also failed to produce opioid-like effects. In morphine-dependent monkeys and rats, acetorphan failed to suppress withdrawal. Additionally, there were no overt withdrawal signs observed following the termination of chronic acetorphan infusion in the rat. Together, these results indicate that acetorphan appears to have minimal abuse potential.

Physostigmine-induced analgesia in young, middle-aged, and senescent rats.

To investigate the effect of aging on cholinergically medicated analgesia, rats from three age groups (3-month, 17-month, and 25-month) were injected with physostigmine (0.0156, 0.0625, or 0.25 mg/kg) or saline. Following the injection, tail-flick latencies were measured at 5-minute intervals for 30 minutes and at 45, 60, 75 and 90 minutes. The analysis of the tail-flick latencies revealed that physostigmine produced a dose-dependent analgesia in all age groups. However, the 17- and 25-month-old age groups were more sensitive to the highest dose of physostigmine. The age-related differences in the analgesia produced by physostigmine is in agreement with other research which has demonstrated that pharmacological stimulation of the cholinergic system produces an equivalent or increased responsivity in aged animals.

Developmental aspects of nociception.

Research has documented the existence of multiple, endogenous systems that modulate nociception. Based on the effects of opioid antagonists and endocrine lesions, endogenous analgesia systems have been organized into four classes: neural-opioid, neural-nonopioid; hormonal-opioid; hormonal-nonopioid. Developmental research on the ontogeny of endogenous analgesic function has revealed differential rates of maturation. Front-paw shock, a stimulus that activates a neural-opioid analgesic response, has been shown to be functionally mature by 28 days of age in the rat. Similarly, hind-paw shock, a stimulus that elicits a neural-nonopioid analgesic response, reaches maturity after two months of age. However, the hormonal-opioid analgesic system activated by cold-water immersion reaches adult levels by 10 days of age. Food deprivation produces a hormonal-opioid analgesic response in adult rats, and food deprivation/isolation of rat pups has been found to elicit an analgesic response in 6-day-old rats. From these data it seems that the rate of development of the different endogenous analgesic systems is related to the activation of neural or hormonal components. Whether the differential rates of development and the neural-hormonal distinction are related to the ecological validity of the activating stimulus remains to be determined.