Renewal of drug seeking by contextual cues after prolonged extinction in rats.

Contextual stimuli associated with drug exposure can modulate various effects of drugs, but little is known about their role in relapse to drug seeking. Using a renewal procedure, the authors report that drug-associated contextual stimuli play a critical role in relapse to drug-seeking previously maintained by a heroin-cocaine mixture (speedball). Rats were trained to self-administer speedball, after which drug-reinforced behavior was extinguished over 20 days in the self-administration context or in a different context. On the test day, rats exposed to the drug-associated context, after extinction in a different context, reliably renewed drug seeking. The authors suggest that the renewal procedure can be used to study mechanisms underlying relapse to drug seeking elicited by drug-associated contextual stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization

The present study was designed to evaluate the relationship between reinstatement of drug-seeking behaviour following long-term extinction of intravenous (i.v.) drug self-administration (an animal model for craving) and long-term behavioural sensitization. Rats were allowed to self-administer heroin (50 microg/kg per inj., 14 daily sessions), cocaine (500 microg/kg per inj., 10 daily sessions) or saline. Following a 3-week extinction period, reinstatement tests were performed to evaluate priming effects of amphetamine, cocaine and heroin on nonreinforced drug-seeking behaviour. In addition, the occurrence of long-term behavioural sensitization in rats with a history of heroin or cocaine self-administration was determined. Heroin-seeking behaviour was reinstated by heroin (0.25 mg/kg), amphetamine (1.0 mg/kg) and cocaine (10 mg/kg). In addition, animals with a history of heroin self-administration displayed locomotor sensitization to both heroin and amphetamine. Cocaine-seeking behaviour was reinstated by cocaine and amphetamine, but not by heroin. Interestingly, locomotor sensitization to amphetamine, but not heroin, was observed in animals with a history of cocaine self-administration. In other words, the induction of drug-seeking behaviour following a prolonged drug-free period was found to be associated with the expression of long-term behavioural sensitization. These data provide experimental evidence for a role of behavioural sensitization in the incentive motivation underlying drug-seeking behaviour. If drug hyperresponsiveness would indeed be a crucial factor in drug-induced craving in human addicts, pharmacological readjustment of the neuroadaptations underlying drug sensitization may prevent relapse to drug use long after detoxification.     

Remission of Ménétrier's disease after a prolonged period with therapeutic eradication of Helicobacter pylori

We report here a case of Ménétrier's disease (MD) that required a prolonged period for remission after eradication therapy of Helicobacter pylori (HP). The appropriate time needed to judge the efficacy of the eradication therapy for HP infection in an MD case is discussed.     

Effects of acute and prolonged opiate abstinence on extinction behaviour in rats.

We examined the role of withdrawal in relapse to drug-seeking and drug-taking by testing the effects of opiate abstinence on extinction behaviour in rats trained to self-administer heroin. Male Long-Evans rats responded for IV heroin under a heterogeneous chain (VI 120 s; FR 1) schedule in which "seeking" responses preceded a "taking" response which produced a drug infusion. Responding was then measured in extinction during acute (6, 12, and 24 hr) and prolonged (3, 6, 12, and 25 day) abstinence. Sucrose consumption and somatic withdrawal were assessed at each testing period. During acute abstinence, responses on the "drug-seeking" manipulandum increased at 24 hr, whereas responses on the "drug-taking" manipulandum increased at 6 hr. Both responses were elevated during the 12-day abstinence test. Sucrose consumption was reduced and somatic withdrawal scores were increased in opiate-experienced rats at each test period. Results suggest that heroin abstinence has different effects on drug-seeking and drug-taking and that these effects do not temporally coincide with somatic measures of opioid withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Explorative and drinking behavior after prolonged access to alcohol and following chronic piracetam administration in mice

Male mice with free access to food, water, and alcohol for 44 weeks were deprived of alcohol for 3 days and then segregated into two groups having (HD) and lacking (LD) the alcohol deprivation-induced elevation in intake. On week 47, the HD and LD groups (divided into subgroups matched for drinking) received either vehicle or piracetam (400 mg/kg) for 10 days. On the last treatment day, alcohol was again withheld. Cross-maze exploration and drinking pattern were evaluated on the first and third postinjection days. Control mice, having had no previous access to alcohol, were subjected to the same treatment and tests. There were a greater number of vehicle-treated HDs displaying arm reentries than LDs or alcohol-naive control mice. Further, the control mice drank less alcohol than HDs during the first 1.5 h of renewal access, and more water than the HD or LD group during the remaining 22.5 h. Piracetam improved maze patrolling and arm reentries in alcohol-naive mice, but did not change these measures in HDs and LDs. No effect of piracetam on drinking parameters was revealed.     

Reinforced alternative behavior during punishment and extinction with rats.

Evaluated the suppressive effect of a reinforced alternative response during extinction and during punishment plus extinction in a discrimination learning paradigm with 36 male hooded rats. Although reinforcement of the alternative response did augment the suppression produced by extinction and by punishment plus extinction, the recovery which resulted when reinforcement for alternative behavior was discontinued eliminated any net reduction in extinction responses. Therefore, under the particular conditions of this study, no significant overall savings in regular extinction or in punished extinction resulted from the temporary reinforcement of alternative behavior. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blockade of the serotonin 5-ht2a receptor suppresses cue-evoked reinstatement of cocaine-seeking behavior in a rat self-administration model.

The serotonin 5-HT2A receptor (5-HT2AR) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT2AR antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in na?ve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT2AR antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001–0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT2AR attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior

cAMP-dependent protein kinase (PKA) in the nucleus accumbens (NAc) has been implicated in cocaine addiction because (1) cocaine reinforcement is mediated by dopamine receptors that modulate cAMP formation, and (2) repeated exposure to cocaine upregulates the cAMP system in NAc neurons. This study tested PKA involvement in cocaine self-administration and relapse of cocaine-seeking behavior by infusing cAMP analogs that activate or inhibit PKA into the NAc of rats. Bilateral intra-NAc infusions of the PKA inhibitor Rp-cAMPS reduced baseline cocaine self-administration, shifted the dose-response curve for cocaine self-administration to the left, and induced relapse of cocaine-seeking behavior after extinction from cocaine self-administration, consistent with an enhancement of cocaine effects in each paradigm. In contrast, pretreatment with intra-NAc infusions of a PKA activator, Sp-cAMPS or dibutyryl cAMP, increased baseline cocaine self-administration during the second hour of testing and shifted the dose-response curve to the right, consistent with an antagonist-like action. After extinction from cocaine self-administration, similar infusions of Sp-cAMPS induced generalized responding at both drug-paired and inactive levers. As an index of PKA activity in vivo, NAc infusions of Rp-cAMPS reduced basal levels of dopamine-regulated phosphoprotein-32 phosphorylation and blocked amphetamine-induced increases in cAMP response element-binding protein (CREB) phosphorylation. Conversely, NAc infusions of Sp-cAMPS increased phosphorylation of CREB. Together, these results suggest that sustained upregulation of the cAMP system in the NAc after repeated cocaine exposure could underlie tolerance to cocaine reinforcement, whereas acute inhibition of this system may contribute to drug craving and relapse in addicted subjects.     

Pretreatment plasma homovanillic acid in schizophrenia and schizoaffective disorder: the influence of demographic variables and the inpatient drug-free period

BACKGROUND: The relationship between plasma homovanillic acid (pHVA) and schizophrenic symptoms has not been conclusively determined. We reexamine pHVA levels in a new sample of patients with emphasis on demographic variables and the drug-free period. METHODS: Plasma HVA levels were studied in 54 schizophrenic and schizoaffective-disordered, drug-free inpatients suffering from a psychotic exacerbation. RESULTS: A significant correlation was observed between pHVA levels and the number of inpatient drug-free days in the total sample, as well as the schizophrenic patient subsample. Further, pHVA was significantly and positively correlated with the duration of illness in the schizophrenic patient subsample. Plasma HVA correlations with behavior, as measured by Brief Psychiatric Rating Scale factors (anxiety/depression and hostility/suspiciousness), emerged only when considering schizophrenic patients drug-free for more than 2 weeks. No correlation was found between pHVA and the age of illness onset or the duration of the delay of treatment of the first psychotic episode. CONCLUSIONS: The effects of antipsychotic withdrawal on levels of pHVA in clinical populations may have to be examined and controlled for in future studies attempting to study the relationship between this metabolite and behavior in acutely ill, drug-free schizophrenic patients.     

Effects of fornix transection and pituitary-adrenal modulation on extinction behavior.

We examined whether the absence of a dynamic pituitary-adrenal response contributes to the behavioral deficit seen in hippocampally damaged rats following the transition to extinction of a learned behavior. In the first experiment, total lever presses and detailed behaviors of rats with fornix-transected and replacement ACTH4–20 or ACTH were compared with the behavior of fornix-transected and sham-transection groups during acquisition and extinction of lever pressing. Fornix-transected rats showed increased resistance to extinction and an altered pattern or mode of extinction responding. ACTH4–20 or ACTH acted similarly in reducing extinction lever presses in fornix-transected rats without altering the mode of extinction responding. In the second experiment the extinction behaviors of rats with fornix transection were compared with those of normal, sham-transection adrenalectomized, or dexamethasone-treated rats. Fornix-transected rats again showed increased resistance to extinction and a different mode of responding during extinction. Adrenalectomized rats showed an extinction deficit but differed from fornix-transected rats. The behavior of dexamethasone-treated rats was similar to that of controls. The results are interpreted to mean that ACTH and corticosterone both affect extinction behavior (in opposite ways) but do not account for the extinction deficit seen in hippocampally damaged rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impulsive choice as a predictor of acquisition of IV cocaine self- administration and reinstatement of cocaine-seeking behavior in male and female rats.

Drug abuse and impulsive choice are related in humans. In female rats, impulsive choice predicted the rate of acquisition of IV cocaine self-administration. The objectives of the present experiments were to: (a) compare impulsive choice in males and females, (b) extend previous research on impulsive choice and acquisition of cocaine self-administration to males, and (c) compare males and females during maintenance, extinction, and reinstatement of cocaine-seeking behavior. Male and female rats were trained on an adjusting delay task in which a response on one of two levers yielded one food pellet immediately, and a response on the other resulted in three pellets after an adjusting delay that decreased after responses on the immediate lever and increased after responses on the delay lever. A mean adjusted delay (MAD) was used as the quantitative measure of impulsivity. In Experiment 1, MADs were analyzed for sex differences. In Experiment 2, acquisition of cocaine self-administration was examined in rats selected for high (HiI; MADs ≤9 seconds) or low (LoI; MADs ≥13 seconds) impulsivity. In Experiment 3, HiI and LoI groups were compared on maintenance and extinction of cocaine self-administration and cocaine-primed reinstatement of drug-seeking behavior. There were no sex differences in impulsive choice; however, HiI male and female rats acquired cocaine self-administration faster than their LoI counterparts. LoI females responded more on a cocaine-associated lever during maintenance and extinction than HiI females, but HiI females showed greater reinstatement of cocaine-seeking behavior than all other groups at the highest dose tested (15 mg/kg). Thus, individual differences in impulsive choice were associated with differences in cocaine-seeking behavior. Impulsive choice and sex may be additive vulnerability factors in certain phases of drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning and extinction of avoidance and escape behavior in neonatal dogs.

Ran 16 neonatal purebred beagles for 6.5 days in a 1-way shuttle box with cold air as the aversive stimulus. 8 Ss started at 1 day of age and 4 each started at 2 and 3 days of age. 8 Ss received escape conditioning and 8 received avoidance conditioning. Following this training, both groups were given a series of extinction trials. Both escape and avoidance conditioning and extinction were obtained. Findings are comparable to previous avoidance findings in neonatal dogs and superior to findings on neonatal mice and kittens. Results display quantitative properties found in studies of adult rats and especially adult dogs. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal and neonatal outcomes after prolonged latent phase

Glycol ethers such as 2-ethoxyethanol (EE) are widely used as solvents because they are miscible in aqueous and organic solutions. Toxic effects of EE in rodents include teratogenicity, fetotoxicity, hematotoxicity, and testicular atrophy. The purpose of this study was to determine the effect of dose on the absorption, metabolism, and excretion of 2-ethoxy [U-14C]ethanol by F344/N rats after inhalation exposure. Rats were exposed to either 5 ppm EE for 5 hr 40 min or 46 ppm EE for 6 hr. The uptake and metabolism of EE were linear in the concentration range studied. Significant percentages of the retained doses were exhaled during (22%) and after exposure (16%) as 14CO2. Forty-six percent of the retained dose was excreted in the urine. Approximately 10% of the retained dose was detected in the carcass 66 hr after exposure. The major urinary metabolite was ethoxyacetic acid (EAA), the toxic metabolite of EE. The amount of EAA excreted was linearly related to exposure concentration. Ethylene glycol and N-ethoxyacetyl glycinate were identified as minor metabolites excreted in the urine. The results of this study suggest that the toxicity of inhaled EE should be directly proportional to the exposure concentration up to 46 ppm if the toxicity of EE is due to EAA.     

Stress relaxation and mechanical behavior of metals

Stress relaxation tests have been made in the temperature range 200° to 400°C on two materials, the Mg-Al eutectic alloy and commercial purity zirconium. The materials represent respectively high and low homologous temperature regimes. The novel features of the tests are the use of high speed, high sensitivity digital measurement techniques and the direct reduction of the data to stress-strain rate curves. It was possible in this way to obtain phenomenological information on the material behavior over a very large range of strain rate with very few specimens. Comparison was made with results obtained by more conventional differential strain rate tests. The test lends itself well to establishing the phenomenology of mechanical behavior of metals.     

Stress responses of horses during a long period of transport in a commercial truck

OBJECTIVES: To characterize progressive patterns of dehydration, stress responses, and water consumption in horses transported long distances in hot weather and to evaluate various measurements in detecting dehydration and stress in transported horses. DESIGN: Prospective study. ANIMALS: 30 mature, healthy horses. PROCEDURE: The following 4 treatment groups were studied: horses that were penned and offered water every 5 hours (n = 5), horses that were penned and not offered water (5), horses that were transported in a truck and offered water every 5 hours (10), and horses that were transported and not offered water (10). The study commenced after 6 hours of water deprivation. Every 4 hours, the truck returned to the pen area and body weights were measured, physical examinations were performed, and blood samples were obtained. During this 1-hour period, water was offered to some horses, depending on treatment group. RESULTS: After 24 hours of transport, 3 horses were judged unable to continue and the study was terminated. Horses that were penned and offered water drank a mean of 38.2 L and horses that were transported and offered water drank 20.9 L, but some of the latter horses did not drink until after 19 or 24 hours of transport. In horses that were transported or penned and not offered water, serum electrolyte concentrations were greater than reference range values by 19 hours. Most horses that were transported and offered water consumed adequate water to postpone severe dehydration beyond 24 hours. CLINICAL IMPLICATIONS: Tame horses in good condition and initially deprived of access of water for approximately 6 hours can be transported in groups in open trailers during hot, humid conditions for up to 24 hours before dehydration and fatigue become severe. Rectal temperature and appearance of the horses were the most useful measures for determining crisis situations.     

Ultrastructural changes in the rat neurohypophysis after a prolonged protein-free diet

The effects on gallbladder contraction of three structurally related peptides, secretin, glucagon and the vasoactive intestinal peptide (VIP) have been compared in urethane-anesthetized guinea pigs. Secretin and glucagon had no effect alone but augmented cholecystokinin (CCK)-induced contractions. VIP decreased CCK-induced contractions.     

Voucher reinforcement for heroin and cocaine abstinence in a outpatient drug-free program.

This study examined an abstinence-contingent voucher incentive program in opiate-dependent clients enrolled in outpatient drug-free (nonmethadone) treatment. Study participants were referred from local detoxification programs and randomly assigned to voucher (n=29) or no-voucher (n=23) conditions. Both groups received intensive cognitive-behavioral counseling; those in the voucher condition could earn up to $1,087.50 over 3 months for submitting urines negative for both opiates and cocaine. Voucher versus no-voucher groups did not differ significantly on mean days retained in treatment (35.9 vs. 39.3 days), mean number of opiate- and cocaine-negative urines submitted (8.3 vs. 6.2), longest duration of continuous abstinence (16.8 vs. 12.1 days), or percentage of participants abstinent for 4 weeks (20.7% voucher vs. 9% no voucher). Possible reasons for negative findings are discussed. Findings suggest that voucher programs must be better tailored to the clinical population and behavioral targets being addressed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The outcome of pregnancy and labor after a period of sterility

In a retrospective study is examine the effect of a previous state of sterility on the outcome of pregnancy and labor. For two years (1993-1994) there were 203 (2.6%) women who gave birth after 6.7% +/- 3.5 years of sterility. From the study are excluded 9 women (4.4%) with multifetal pregnancies and 13 cases (6.4%) with different diseases, which may adversely affect the pregnancy of the foetus. In the study group of 181 primiparous women the rate of premature labor is 2.2% which is significantly lower than the hospital incidence (11%) for the same period. The cesarean section (CS) rate after period of sterility is unreasonably high--69%. In the subgroup scheduled for vaginal labor CS are performed in 34% of cases. The indications for the elective CS are complex, less justifiable and partially due to non medical reasons. The past period of sterility has not adverse effect on the course of the vaginal labor or the state of the newborn at delivery.     

Recovery after prolonged cross-clamping tepid blood cardioplegia: report of a case

Despite a prolonged repetitive aortic cross-clamp time of 411 min, a patient who suffered a left ventricular rupture after undergoing mitral valve replacement following mitral valvuloplasty and Maze procedure recovered without any permanent residual left ventricular dysfunction. During the aortic cross-clamping we used tepid blood cardioplegia for myocardial protection. This case report serves to demonstrate the potential of tepid blood cardioplegia as an effective method of myocardial protection.