Effects of proposed treatments for cocaine addiction on hemodynamic responsiveness to cocaine in conscious rats

Several agents may treat cocaine addiction and toxicity including bromocriptine, desipramine, GBR 12909 [1-(2-(bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl) piperazine], diazepam, buprenorphine and dizocilpine. In this study, we sought to determine whether these specific therapeutic agents alter cardiovascular responses to cocaine in conscious rats. Arterial pressure responses to cocaine (5 mg/kg, i.v.) were similar in all rats whereas cardiac output responses varied widely. In 26 of 33 rats (named vascular responders), cocaine induced a decrease in cardiac output of 8% or more. The remaining rats with little change or an increase in cardiac output were classified as mixed responders. Pretreatment with bromocriptine (0.1 mg/kg) or desipramine (1 mg/kg) increased cardiac output in mixed responders and increased systemic vascular resistance in vascular responders similar to the differential effects noted with cocaine. GBR 12909 (0.5-10 mg/kg) elicited a decrease in cardiac output at higher doses. Diazepam (0.1 and 0.5 mg/kg) had small, short-lasting effects on cardiovascular parameters. Buprenorphine (0.3 mg/kg) or the NMDA (N-methyl-D-aspartic acid) receptor antagonist, dizocilpine (0.05 mg/kg), increased arterial pressure, heart rate and cardiac output in vascular responders. Bromocriptine and desipramine prevented the difference in cardiac output responses in vascular and mixed responders by reducing the cocaine-induced decrease in cardiac output in vascular responders. Pretreatment with GBR 12909 (1 mg/kg) had little effect on cardiovascular responses to cocaine except to depress the increase in cardiac output noted in mixed responders. Buprenorphine selectively enhanced the increase in systemic vascular resistance whereas dizocilpine enhanced the pressor response. These data suggest that several treatment regimens for cocaine addiction alter the cardiovascular responses to cocaine and that dopamine D2 receptor activation may be necessary for the decrease in cardiac output noted in vascular responders.     

Effects of prior group memberships on subsequent reconnaissance activities.

1,134 college freshmen completed an orientation questionnaire assessing their experiences in high school groups and expectations about college groups. 220 Ss were also interviewed later about their behavior toward campus groups at an activities fair. Ss whose experiences in high school groups were more positive tried harder to identify potentially desirable college groups, primarily because they believed that belonging to such groups would be useful for achieving personal goals. Ss with prior experience in relevant high school groups used that experience to evaluate similar college groups and thus made more realistic (less optimistic) evaluations of those groups than did Ss without prior experience. Among Ss who wanted to join a college group, those who had belonged to a relevant high school group behaved differently at the activities fair than did those who had not. Ss with prior experience were more likely to approach their chosen group at the activities fair and to avoid other groups there of a similar sort. (52 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitative and disruptive effects of prior exposure to shock on subsequent avoidance performance.

Subjected 40 male rats from each of 5 strains to 10 signaled inescapable 1-ma shock presentations. Shock facilitated subsequent 1-way and shuttle-avoidance performance (1-ma shock) in Charles River hooded, Wistar, Holtzman, and Sasco Ss, but did not significantly affect avoidance learning in Sprague-Dawley Ss. A 2nd experiment employing 120 male Holtzman rats indicated that inescapable shock of 1 ma. facilitated subsequent 1-way and shuttle-avoidance performance, while exposure to shock of 2 ma. facilitated 1-way and interfered with shuttle-avoidance performance. Movement ratings recorded during both CS and intershock intervals in pretraining were found to be good predictors of subsequent avoidance performance in preshocked Ss. Results are interpreted in terms of response repertoire changes produced by shock in conjunction with the defense reaction necessary in acquiring the avoidance response. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal cocaine exposure on embryonic expression of sonic hedgehog

PURPOSE: To estimate the impact of visual impairment in older Australians on the use of community support services. METHODS: In the Blue Mountains Eye Study, 3654 people aged 49 or older were examined- 82.4% of eligible residents in an area west of Sydney, Australia. Presenting and best-corrected visual acuities were measured using a LogMAR chart. Subjects were categorized as having visual impairment if their better eye read 40 or fewer letters (20/40 or worse). Interview data included marital and other socioeconomic status measures, living status (alone or with spouse or other person), use of community support services, reliance on regular help from nonspouse family members or friends, and perceived ability to go out alone. RESULTS: After adjusting for age, gender, education, living status, walking disability, and health-related factors, for each one-line (five-letter) decrease in best-corrected visual acuity, there was a corresponding increase in reliance on community support services (odds ratio [OR], 1.17; 95% confidence interval, [CI] 1.07-1.28) or combined community and family support (OR 1.22; 95% CI, 1.12-1.32). Visually impaired persons were three times as likely to use regular support services provided by the municipality (OR 3.1; 95% CI, 1.8-5.1). A similar increased reliance on regular help from community, nonspouse family members, or friends was found. Visually impaired persons were also much more likely to state that they thought they were unable to go out alone (OR 6.2; 95% CI, 2.6-14.3). The findings were similar when presenting visual acuity was used to define visual impairment or after subjects with walking disabilities were excluded. Visual impairment seemed to have a greater effect on use of community support services in women than in men. CONCLUSIONS: After adjustment was made for confounding factors, visual impairment was found to affect significantly and negatively the independence of elderly people, particularly older women. Presenting visual acuity closely approximated best-corrected visual acuity in its impact on the use of community support services.     

"Facilitative and disruptive effects of prior exposure to shock on subsequent avoidance performance": Erratum.

Reports an error in "Facilitative and disruptive effects of prior exposure to shock on subsequent avoidance performance" by H. Anisman and T. Waller (Journal of Comparative and Physiological Psychology, 1972[Jan], Vol 78[1], 113-122). On page 114, the sentence beginning on Line 56, Column 2, should read: "Thirty seconds after placement in the compartment one half of the rats were given 10 CS (light and tone) presentations in which the CS was 9 sec. in duration, while the remaining rats received 10 CS-US presentations in which the US was a 1-ma. shock (constant current, ac) 2 sec. in duration." (The following abstract of this article originally appeared in record 1972-22565-001.) Subjected 40 male rats from each of 5 strains to 10 signaled inescapable 1-ma shock presentations. Shock facilitated subsequent 1-way and shuttle-avoidance performance (1-ma shock) in Charles River hooded, Wistar, Holtzman, and Sasco Ss, but did not significantly affect avoidance learning in Sprague-Dawley Ss. A 2nd experiment employing 120 male Holtzman rats indicated that inescapable shock of 1 ma. facilitated subsequent 1-way and shuttle-avoidance performance, while exposure to shock of 2 ma. facilitated 1-way and interfered with shuttle-avoidance performance. Movement ratings recorded during both CS and intershock intervals in pretraining were found to be good predictors of subsequent avoidance performance in preshocked Ss. Results are interpreted in terms of response repertoire changes produced by shock in conjunction with the defense reaction necessary in acquiring the avoidance response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic ethanol exposure on oxidation and NMDA-stimulated neuronal death in primary cortical neuronal cultures

Two enzymes of detoxification were studied in blood samples from 27 patients with ulcerative colitis (UC) and 18 controls to determine whether there is an abnormality in sulfur metabolism in UC. Thiol methyltransferase (TMT) activity was measured in erythrocyte membranes as the extent of conversion of 2-mercaptoethanol to S-methyl-2-mercaptoethanol with [3H]methyl-S-adenosyl methionine as methyl donor. Phenol sulfotransferase (PST) activity was measured in platelet homogenates as the extent of sulfation of p-nitrophenol with 3-phosphoadenosine 5-phospho[35S]sulfate (PAPS) as sulfate donor. TMT activity was significantly higher in UC patients (27.0 vs 17.1 nmol/mg protein/hr; P < 0.005). No difference in PST activity was found. We conclude that TMT may be up-regulated in UC to detoxify excess hydrogen sulfide exposed to the peripheral blood compartment. This may arise from either increased luminal sulfide production or reduced colonic detoxification.     

Effects of testosterone propionate treatment of neonatally ovariectomized rats on growth and subsequent responsiveness to oestrogen

There was no significant difference in body weight between neonatally ovariectomized (OvX) rats whether given oil treatment or 90 mug testosterone propionate (TP) on day 3, when examined up to 23 weeks of age. When these two animals were injected with oestradiol benzoate (3 mug/day for 2 weeks), the neonatally OvX TP treated rats showed a significantly smaller depression in body weight than did the control neonatally OxX rats. Measurement of food intake also showed that TP treated rats responded significantly less to the depressant effects of oestrogen than did the controls. These data are consistent with the hypothesis that the ovary does restrain body weight in TP rats but that androgen treatment in the neonatal period may not have a specific effect on growth but may alter the sensitivity of growth regulating processes to the inhibitory effects of oestrogen.     

Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats.

Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous/ly (sc) injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8–20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the 1st 10 responses and made significantly more errors before the 1st reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to cocaine on Morris water maze performance in adult rats.

The spatial memory of adult rats prenatally exposed to cocaine and that of control offspring was assessed using the Morris water maze. Offspring were derived from Sprague Dawley dams that received subcutaneous injection of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. After acquisition, the platform was moved to a new location (reversal phase). Probe trials were conducted at the end of acquisition and reversal training. On the 1st acquisition day, adult male and female offspring prenatally exposed to cocaine required significantly more time and traversed a greater distance to find the hidden platform than did control offspring. Despite these initial differences observed in C40 offspring performance, all of the rats were performing at equivalent levels at the time probe trials were conducted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prognostic significance of prior preterm twin delivery on subsequent singleton pregnancy

OBJECTIVE: Our purpose was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy. STUDY DESIGN: The Medical University of South Carolina perinatal database was accessed to identify a cohort of patients who were delivered of twins followed by a singleton gestation (1981 to 1993). Maternal transports were excluded to minimize referral bias. Preterm birth was defined as < 37 weeks' gestation. Relative risks with 95% confidence intervals were calculated. RESULTS: One hundred forty-four patients were identified who were delivered of twins followed by a singleton gestation. Preterm delivery occurred in 86 (59.7%) of the twins and 21 (14.6%) of the subsequent singletons. Preterm birth of twins was associated with a significantly increased risk of preterm delivery in a subsequent singleton pregnancy (relative risk 2.87, 95% confidence interval 1.02 to 8.09). In the subset of women who were delivered of twins at < 30 weeks' gestation, 42% of the subsequent singletons were delivered preterm (relative risk 6.11, 95% confidence interval 2.07 to 18.02). The relative risk of preterm birth of a singleton after delivery of twins between 30 and 34 weeks' gestation was 3.63 (95% confidence interval 1.02 to 12.92). However, if the preceding twins delivered between 34 and 37 weeks' gestation, the relative risk of preterm birth of the subsequent singleton was not significantly increased (relative risk 1.42, 95% confidence interval 0.40 to 5.01). CONCLUSIONS: Preterm birth of twins before 34 weeks' gestation is associated with a significant risk for preterm delivery in a subsequent singleton pregnancy. The magnitude of risk increases with decreasing gestational age of the preceding twin delivery.     

Effects of oral cocaine on intravenous cocaine discrimination in humans.

This study was designed to evaluate the drug discrimination paradigm as a model for assessing the ability of potential agonist medications to block the effects of intravenous cocaine. Previous research has demonstrated that oral cocaine attenuated the subjective and physiological effects of intravenous cocaine injections, and in the absence of a known efficacious medication for cocaine use disorders, a proof-of-concept approach was used in which cocaine was acutely administered orally to block intravenous cocaine's discriminative-stimulus effects. During training, 11 cocaine-dependent participants were able to discriminate between intravenous saline and 20 mg/70 kg iv cocaine, and 8 of these participants completed the study. After training, participants ingested capsules containing either placebo or 300 mg/70 kg cocaine 60 min prior to the intravenous injection of different doses of cocaine during test sessions with no contingencies in place. Each cocaine dose was administered twice, once under each oral pretreatment condition. Training sessions were interspersed among the test sessions. Physiological and subjective effects were measured throughout each session. Oral cocaine moderately increased some of the subjective and physiological effects of the lower doses of intravenous cocaine, whereas effects at the higher doses were unaltered. Similar changes were seen for the discrimination results. Thus, although oral cocaine given acutely likely is not a viable treatment medication for cocaine dependence, the usefulness of the drug discrimination model in the evaluation of agonist treatment medications remains unclear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of acute and delayed effects of prior chronic cocaine administration on regional rates of cerebral protein synthesis in rats

Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPSleu) measured with the [1-14C]leucine method. A single dose of cocaine to naive rats reduced ICPSleu by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion (P = .0003). A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPSleu. Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPSleu was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPSleu was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex (P < .006). These results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPSleu are distinctly different and occur in different regions of the brain.     

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.     

In utero cocaine exposure and language development

A growing body of literature suggests that in utero cocaine exposure may place a child at risk for impaired language development. Because the field of gestational drug exposure and its effects on communicative development is young, the research is still limited and the data are contradictory, plagued by many methodological problems. The accumulating evidence, however, suggests that the development of specific aspects of language may be compromised in a percentage of children and that outcome is affected by a wide range of prenatal and postnatal biological and environmental factors. The data also suggest that deficits are best identified through the use of focused test batteries and may be evident only under stressful or difficult conditions. This article provides a critique and general overview of the literature on the early communicative and language development of prenatally cocaine-exposed children. Potential reasons for compromised language development and the clinical implications of these findings are discussed.     

Effects of crack cocaine on neurocognitive function

Because crack cocaine appears to have a preferential effect on the metabolic and electrophysiological activity of the frontal and temporal regions of the brain (Pascual-Leone et al., 1991a, 1991b; Volkow, 1992), we hypothesized that cognitive measures of those regions would be impaired in crack cocaine users relative to measures in normal volunteers. We used logistic regression to determine the relationship of cocaine usage to neuropsychological test performance. We compared 38 patients with an average of 3.6 (SD = 2.5) years of crack cocaine use and 24.5 (SD = 28.1) days of abstinence to 54 normal volunteers on a battery of neuropsychological tests. Statistical adjustments were made for the effects of age, education, socioeconomic class, and level of depression. Our findings were mixed with regard to purported measures of executive/frontal functioning, with worse performance associated with cocaine usage on the Booklet Categories Test, but better performance associated on others (number of categories on the Wisconsin Card Sorting Test, Controlled Oral Word Association). Cocaine usage was associated with impairment on measures of spatial, but not verbal memory, confrontation naming, and Trail-making Test, Part B, a measure of perceptual-motor speed and cognitive flexibility. In summary, it appears that continuous crack cocaine use produces a dissociative pattern in neuropsychological test performance with improvement on some measures, but deterioration on others. The permanence of these effects remains to be determined with longitudinal studies.     

Effects of prior exposure on conditioned taste aversion in the rat: Androgen- and estrogen-dependent events.

Studied the effects of preexposure and gonadal hormone manipulation on the extinction of a conditioned taste aversion in 198 male Sprague-Dawley rats. In Exp I, Ss were given 1 prior exposure to sucrose at some selected time (Days 4, 2, or 1) before a 2nd exposure (Day 0) to sucrose and a LiCl injection, or they were given only a single exposure (Day 0). Under single exposure, castrated Ss extinguished the aversion faster than either testosterone-treated castrated Ss or sham-operated Ss. In Exp II, estradiol, dihydrotestosterone, and testosterone were studied by using only a Day 1 preexposure condition. The testosterone-treated group maintained the aversion for the longest period, followed by dihydrotestosterone-treated, sham, castrated, and estradiol-treated groups. In Exp III, estradiol was administered alone or in combination with 2 doses of dihydrotestosterone. Findings indicate that the outcome of behavior was dependent on the ratio of estradiol to dihydrotestosterone, with variations in this ratio resulting in fast (estrogen effect) to slow (androgen effect) rates of extinction. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine.

Adult male rats gestationally exposed to cocaine and nonexposed control offspring were examined for differences in operant responding for cocaine and sucrose reinforcement. Offspring were derived from dams that had received subcutaneous injections of 40 mg/kg/3cc cocaine hydrochloride daily on gestational Days 8–20 and nontreated control dams. Although no prenatal treatment differences were seen when the animals lever pressed for sucrose pellets on a progressive-ratio (PR) schedule, adult offspring prenatally exposed to cocaine were observed to exhibit an enhanced rate of cocaine intravenous self-administration on a fixed-ratio 5 (FR-5) schedule along with a marked decrease in break point on the PR reinforcement schedule. These results suggest that the reinforcing efficacy of cocaine may be reduced in animals with a prenatal history of cocaine exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)