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)     

Chronic cadmium exposure alters cocaine self-administration in adult male rats.

Adult male rats (Rattus norvegicus) were exposed to a water supply in the home cage containing 100 ppm cadmium chloride and sodium saccharin (.65% wt/vol; cadmium group) or water containing only the saccharin amendment (group control). On Day 65 of exposure, animals from each group received jugular catheter implants and were subsequently trained over the course of 15 daily 2-hr sessions to self-administer a .25 mg/kg/infusion of cocaine HCl under a fixed ratio 1 schedule. Immediately following acquisition training, the full dose-effect function was determined for all animals by using cocaine doses of .03, .06, .125, .25, .50, and 1.0 mg/kg. Cadmium-exposed animals executed more active (cocaine) lever responses during acquisition training but were not different from controls in depressing a pharmacologically inactive lever. For dose-effect testing, cadmium exposed animals exhibited greater self-administration than controls at the higher doses of cocaine, and there was evidence that the cocaine dose that produced maximum responding was higher in cadmium-exposed than control animals. (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.     

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)     

Enduring effects of prenatal cocaine exposure on attention and reaction to errors.

Rats exposed to cocaine prenatally were administered a series of 3-choice visual attention tasks, with the most pronounced deficits seen in a task in which the onset time, location, and duration of a visual cue varied unpredictably between trials. The cocaine-exposed rats were less accurate than controls but did not differ in the rate of premature responses or omission errors. The pattern of errors, coupled with response latency data, implicated deficits in the ability to rapidly engage attention and maintain a high level of alertness to the task. The cocaine-exposed rats also exhibited a blunted reaction to an error on the previous trial, possibly reflecting an alteration in emotional regulation and/or error monitoring. Implications for underlying neuropathology are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early postnatal X-irradiation of the hippocampus and discrimination learning in adult rats.

Trained Long-Evans rats with X-irradiation produced degranulation of the hippocampal dentate gyrus in the acquisition and reversal of simultaneous visual and tactile discriminations in a T-maze in 3 experiments. The experiments employed the same treatment, apparatus, and procedure but varied in task difficulty. In the brightness and roughness discriminations, the irradiated Ss were not handicapped in acquiring or reversing discriminations of low or low-moderate task difficulty. However, these Ss were handicapped in acquiring and reversing discriminations of moderate and high task difficulty. In a Black/White discrimination in which the stimuli were restricted to the goal-arm walls, the irradiated Ss were handicapped in the acquisition (low task difficulty) and reversal (moderate task difficulty) phases of the task. Results suggest that the irradiated Ss were not handicapped when the noticeability of the stimuli was high, irrespective of modality used, but were handicapped when the noticeability of the stimuli was low. Results are consistent with the hypothesis that rats with hippocampal damage are inattentive due to hyperactivity. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats

Pregnant rats (Mol:WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their physical development was delayed. Neurobehavioral evaluation of the male pups revealed no effects on basal functions of the central nervous system. The animals appeared normal and motor function (rotarod), activity level (open field), and performance in learning tasks with a low grade of complexity were similar in the two groups. However, in more difficult tasks such as the reversal procedure in Morris water maze and operant delayed spatial alternation (Skinner boxes), performance was impaired in exposed offspring.     

Context as a conditional cue in operant discrimination reversal learning.

Five experiments with 68 pigeons investigated the conditions under which contextual stimuli gain conditional control in the discrimination reversal paradigm. In Exp I, Ss learned an operant discrimination in which the positive stimulus (S+) was 555 nm and the negative stimulus (S–) was 576 nm in one context (houselight off plus white noise [HLFN]) and then learned the reversal (S+ 576 nm; S– 555 nm) in another context (houselight on plus tone [HLNT]). Subsequent wavelength generalization testing revealed responding appropriate to each context: The gradients peaked at 555 nm in HLFN and at 576 nm in HLNT. In Exp II, separate groups experienced both visual and auditory context cues, only visual ones, or only auditory ones. The visual cues worked as well as the compound, but the auditory cues gained no conditional control. In Exp III, houselight illumination replaced by white light directly added to the colors serving as discriminative cues. Results suggest that houselight illumination does not gain conditional control by altering the brightness and saturation of the key colors. In Exp IV, HLNT and HLFN gained conditional control over discriminations based on different angles of a white line, but background key color did not. In Exp V, conditional control over a color discrimination was established by contexts consisting of black and white striped walls vs plain walls. Findings suggest that pigeons use diffuse visual cues to identify the place where food-reinforced learning has taken place. (16 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Enrichment to odors improves olfactory discrimination in adult rats.

The authors tested how prior odor enrichment affects the spontaneous discrimination of both preexposed and novel odors. Experimental rats were exposed to single odors or to pairs of similar or dissimilar odors for 1-hr periods twice daily over 20 days. Spontaneous discriminations between pairs of similar odors were tested before and after the odor exposure period using an olfactory habituation task. The authors found that (a) experimental rats did not spontaneously discriminate similar odor pairs before the exposure period, whereas they spontaneously discriminated them after the enrichment period, and (b) the improvement of performance was not selective for the odors used during enrichment. These results show that odor experience changes perception in the manner predicted based on other groups' electrophysiological experiments. (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.     

Blood ethanol concentration from early postnatal exposure: Effects on memory-based learning and hippocampal neuroanatomy in infant and adult rats.

Early postnatal exposure to ethanol (ETOH) that results in daily high-peak blood ethanol concentration (BEC) retarded the acquisition of single-patterned alternation (PA), a kind of memory-based discrimination learning, and was related to reduced brain weight, hippocampal cell number, and CA1 area in infant rats. These behavioral and neuroanatomical effects survived into young adulthood. On the PA discrimination, in both pups and young adults, postnatal exposure to high-peak ETOH conditions, in relation to low-peak and control conditions, impaired the acquisition of PA at 60-sec but not at 30-sec intertrial intervals. These results provide further evidence of hippocampal involvement in intermediate-term memory and indicate that early postnatal ETOH is a behavioral and neuroanatomical teratogen, particularly when the BEC is relatively high. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement and retardation of discrimination learning in chicks after exposure to the discriminanda.

Used an imprinting procedure to expose groups of Ross domestic chicks (N = 57) to 1 or 2 moving objects on Days 1-5 after hatching for a total of 30 or 100 min. From Day 8-12 Ss were given a discrimination learning task. Ss exposed to 1 of the discriminanda learned the task in fewer trials than Ss exposed to neither. However, Ss that had been exposed to both stimuli took many more trials to reach criterion than Ss that had seen neither in the imprinting situation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal ethanol exposure on parvalbumin-expressing GABAergic neurons in the adult rat medial septum

Exposure of human fetuses to ethanol often results in the fetal alcohol syndrome. Animal models of fetal alcohol syndrome have been developed and used to examine the consequences of prenatal ethanol exposure on the central nervous system. The objective of this study was to determine the long-term effects of prenatal ethanol exposure on parvalbumin-expressing (PA+) GABAergic neurons of the rat medial septum. Pregnant Long-Evans rats were maintained on 1 of 3 diets from gestational day 0 to 21: an ethanol-containing liquid diet in which ethanol accounted for 35% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, or a lab chow control diet. Offspring were killed on postnatal day 60, and their brains were prepared for parvalbumin immunocytochemistry. Female rats exposed to the ethanol-containing diet during gestation had 42% fewer PA+ neurons in the medial septum and reduced PA+ cell density when compared with female rats exposed to the sucrose diet. Ethanol females also had fewer PA+ neurons per unit volume than sucrose females. Male rats exposed to ethanol did not display a similar reduction in PA+ neurons or density. No effect of prenatal diet was found on the area or volume of the medial septum, nor were cell diameters affected. As such, prenatal exposure to ethanol seems to reduce permanently the number of PA+ neurons in the female rat medical septum without affecting area, volume, or neuronal size. Functional implications and possible relations to the fetal alcohol syndrome are discussed.     

Automated study of simultaneous-cue olfactory discrimination learning in adult mice.

Adult C57BL/6J mice were trained in a fully automated operant task to discriminate between 2 simultaneously presented odors for water reward. Each mouse was trained on 16 different discrimination problems to a criterion of 90% correct in a block of 20 trials for each problem. Each of the mice tested reached criterion on all discriminations; the number of errors made before reaching criterion was greatest for the first few problems and decreased substantially thereafter. Acquisition performance on early trials of novel discriminations suggested that mice form learning sets for olfactory cues. The mice were trained on 4 additional problems and tested for memory with probe trials at retention intervals of 1, 2, 4, and 8 weeks. Good retention of olfactory cues was seen even at the longest memory delay. Automated testing of olfactory discriminations should be useful for assessing learning and memory abilities in genetically modified mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay of reinforcement in instrumental discrimination learning of rats.

Assigned 4 groups of 8 male albino rats each to a 2-choice discrimination task. Ss were reinforced for pressing 1 lever in the presence of 1 auditory stimulus and for pressing an alternative lever in the presence of a 2nd auditory stimulus. Acquisition of the discrimination was retarded when reinforcement was delayed for all or a random half of the correct responses in the presence of each stimulus. However, performance was facilitated when reinforcement was delayed for all of the correct responses in the presence of 1 stimulus but not the other. Results are interpreted in terms of both classical and operant mediational processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intravenous cocaine discrimination in humans.

Ten cocaine-dependent participants were trained to discriminate between intravenous saline and 20 mg/70 kg cocaine. During the first session, saline and cocaine injections were alternated twice, with each separated by 1 hr. The injections were identified by letter codes. During the next 3 sessions, 12 trials were conducted, with saline and cocaine administered 6 times each in pseudorandom order. Thirty minutes following each injection, participants were asked to identify the injection by letter code. Seven of the 10 learned the discrimination (at least 10 trials correct). To evaluate sensitivity, the investigators tested participants with different doses of cocaine in test sessions. In the next phase, methamphetamine (5 and 10 mg/70 kg) and pentobarbital (50 and 100 mg/70 kg) were given intravenously during test sessions to determine whether the discrimination exhibited pharmacological class selectivity. During the evaluation of sensitivity and selectivity, training sessions were interspersed. As dose of cocaine increased, the number of participants identifying the test dose as cocaine increased, demonstrating sensitivity. The higher doses of methamphetamine and pentobarbital substituted for cocaine. The physiological and subjective effects of cocaine and methamphetamine were stimulant-like and dose related. Pentobarbital produced no physiological changes but increased Visual Analog Scale ratings of Sedation, Good Drug Effect, and High. This failure to demonstrate pharmacological selectivity may be related to participants' learning a drug-vs.-no-drug discrimination, and thus it may be necessary to alter training procedures in future studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of infantile undernutrition on adult learning in rats: Methodological and design problems.

Examines research bearing upon possible confounding variables involved in the study of the effects of early undernutrition upon later learning in rats. The procedures currently used to produce undernutrition also produce changes in the infant rats' social and environmental conditions. Evidence from other sources indicate that these types of changes may play an important role in the determination of later behavior. Attribution of the causes of later effects of undernutrition must be reinterpreted in light of this evidence. Early undernutrition and the variables confounded with it produce effects on later size, motor ability, behavior toward food, ability to absorb and use food and to adjust to food deprivation, and responsibility to aversive and environmental stimuli. Thus, the effects of undernutrition upon later learning may be due to the effects upon these other variables which can affect learning performance rather than upon learning capacity. Strategies for dealing with these problems depend upon the goals of the researcher. (86 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Neonatal exposure to cocaine enhances the reward-potentiating properties of the drug in young adult animals.

Either cocaine (20 mg/kg) or saline vehicle was administered to rat pups once daily on postnatal days 1–8. The enhancement of braid stimulation reward (BSR) by acute administration of cocaine (2.5, 5, and 10 mg/kg ip) was assessed in adult offspring (70–90 days of age) using a rate-frequency curve-shift paradigm. Acute administration of cocaine produced orderly dose-related shifts of the rate-frequency function toward lower frequencies in all groups indicating a reward-enhancing effect of the drug on BSR. However, offspring neonatally exposed to cocaine displayed a greater drug-induced potentiation of BSR. Of particular note, the small but significant enhancement of the reward-potentiating properties of cocaine was more pronounced in female offspring neonatally exposed to the drug. These findings indicate that the rewarding properties of cocaine were altered by neonatal exposure to the drug in a sexually dimorphic fashion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)