Search Results - (Author, Cooperation:R. Spanagel)

2015-06-13

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adolescent ; Adult ; Animals ; Brain/metabolism/*physiology ; Female ; Gene Expression ; Humans ; Ion Channels/*genetics ; Magnetic Resonance Imaging ; Male ; Mice ; Nerve Net/metabolism/*physiology ; Neural Pathways/metabolism/physiology ; Polymorphism, Genetic ; Rest/*physiology ; Synapses/metabolism/physiology ; *Transcriptome ; Young Adult

2018-06-22

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Geosciences

Computer Science

Medicine

Natural Sciences in General

Physics

Neuroscience

1749-6632

Blackwell Publishing Journal Backfiles 1879-2005

Natural Sciences in General

Electronic Resource

1433-0407

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-2072

Key words Acamprosate ; Dopamine ; Heroin self-administration ; Nucleus accumbens ; Reinstatement ; Relapse ; Sensitization ; Stress

Springer Online Journal Archives 1860-2000

Medicine

Abstract Acamprosate (calcium-acetyl homotaurinate) is a new compound used in the treatment of alcohol abuse. Because of the putative link between alcoholism and the endogenous opioid systems in both humans and laboratory animals, we tested in rats the effects of acamprosate on behavioral and neurochemical effects of opioid drugs related to their abuse potential. These included sensitization to the behavioral effects of morphine, morphine-induced dopamine (DA) release in the nucleus accumbens (NAS), intravenous (IV) heroin self-administration and relapse to heroin seeking in drug-free rats. In experiment 1, rats were injected daily with either morphine (10 mg/kg, SC) or saline for 14 days. Three days later in a test for the expression of sensitization, an injection of morphine (10 mg/kg) resulted in increased locomotor activity and enhanced DA release in the NAS in rats previously exposed to morphine. Acamprosate (two injections of 200 mg/kg; 12 h apart; IP) suppressed the expression of the sensitized responses, but did not alter the effects of morphine in drug-naive control rats. In experiment 2, it was found that acamprosate (two injections of 50–200 mg/ kg; IP) had no consistent effects on IV heroin self-administration (50–100 μg/kg per infusion) and, in experiment 3, that acamprosate (100–200 mg/ kg, IP) did not alter reinstatement of drug seeking induced by priming injections of heroin (0.25 mg/kg, SC) or a footshock stressor (15 min; 0.5 mA) after a 5- to 8-day period of extinction. Thus, although acamprosate attenuated the expression of sensitized locomotor activity and DA release in the NAS, it did not have any consistent effect on either the intake of heroin during the maintenance phase or the relapse to heroin seeking in a drug-free state. Thus, to the extent that the self-administration and the reinstatement procedures provide valid preclinical models for drug use and relapse in humans, our data suggest that acamprosate may not be effective in altering drug-taking behavior in heroin users.

Electronic Resource

1432-2072

Microdialysis Conditioned place preference ; Morphine Locomotor activity ; Genetic differences ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Abstract Studies examining differential sensitivity to psychoactive drugs in mice suggest that genotype may play a critical role. Furthermore, an involvement of genotype in mediating individual differences in sensitivity to the rewarding effects of several drugs of abuse has also been postulated. The aim of this study was to examine the conditioned rewarding and dopamine-releasing effects of morphine in two outbred rat strains commonly used in addiction research. Additionally, the behavioural and neuroendocrine responses of these strains to the stress of novelty were also examined. Basal locomotor activity was higher in Wistar rats than Sprague-Dawley following exposure to a novel environment. In contrast, elevations in plasma corticosteroid levels following novelty exposure did not differ between the two strains. In a counterbalanced place preference conditioning procedure, increasing doses of morphine (1.0–10.0 mg/kg SC) produced significant conditioned place preferences (CPP) in both Wistar and Sprague-Dawley strains. However, Wistar rats required a significantly larger dose of morphine (5.0 mg/kg) to produce a significant CPP than the Sprague-Dawley rats. In the latter strain, CPP occurred with doses of 3.0 mg/kg and greater. In parallel microdialysis experiments, both strains showed significant dose-related increases in dopamine release in the nucleus accumbens following acute morphine challenge (1.0–10.0 mg/kg SC). Again in Wistar rats, a larger dose of morphine was necessary to produce a significant increase in comparison to Sprague-Dawley rats. These results show that genetically distinct rat strains can show differential sensitivity to opioids, more specifically to drug-seeking responses.

Electronic Resource

1432-2072

Anxiety ; Elevated plus-maze ; Ethanol ; Oral self-administration ; Tension-reduction hypothesis ; Individual differences

Springer Online Journal Archives 1860-2000

Medicine

Abstract Anxiolytic effects of ethanol have been proposed to be important factors in the initiation of ethanol consumption. To examine this hypothesis, drug-naive Wistar rats were tested in the elevated plusmaze to determine their initial level of anxiety. Based on their response, we separated the animals into anxious and non-anxious groups. After that, animals went through an oral ethanol self-administration procedure. Rats that were initially classified as anxious showed a significantly (P〈0.01) higher intake and preference for ethanol during the initiation phase of the voluntary drinking procedure than non-anxious animals. In another experiment, intraperitoneal (IP) injections of ethanol (0.5–1.5 g/kg) produced dose-dependent anxiolytic effects in rats when tested in the elevated plus-maze procedure. Blood ethanol levels following IP injections during the plus-maze test were similar to those reached during the oral ethanol self-administration procedure, which shows that the rats indeed drank sufficient amounts of ethanol to experience its anxiolytic effects. These findings indicate that the basal level of anxiety plays an important role in vulnerability to alcohol drinking.

Electronic Resource

1435-1463

Keywords: Alcoholism, craving, relapse, acamprosate, naltrexone.

Springer Online Journal Archives 1860-2000

Medicine

Summary. A new animal model of alcoholism has been developed. Rats derived from this model show certain characteristics: (i) they have an incentive demand to consume alcohol, (ii) they exhibit relapse-like drinking even after a very long time of abstinence, (iii) they show tolerance to alcohol and have mild signs of physical withdrawal during the onset of abstinence, and (iv) during abstinence they also exhibit a psychological withdrawal syndrome consisting of enhanced anxiety-related behaviour and hyperreactivity to stressful situations. Anti-craving drugs such as acamprosate and naltrexone which proved to be effective in human alcoholics to prevent relapse were also effective in our animal model. Thus, both compounds suppressed the alcohol deprivation effect which is used as a measure for craving and relapse. It is concluded that this pharmacological validation of our model demonstrates the predictive value of our model and enables us to further characterize putative anti-craving drugs and neurobiological mechanisms of addictive behaviour.

Electronic Resource