Nicotine exposure throughout early development promotes nicotine self-administration in adolescent mice and induces long-lasting behavioural changes.

Maternal cigarette smoking during pregnancy can result in behavioural problems of the offspring. Although the causative agent in tobacco smoke that leads to these aberrations is not known, some studies using animal models have supported the hypothesis that nicotine may cause impairments in fatal and neonatal development. However, in many of the animal studies nicotine has been administered by subcutaneous injections, which could lead to significant fetal hypoxia; some routes of drug administration included stressful procedures to pregnant dams that could create unfavorable fetal environment.

Effect of forced chronic oral nicotine exposure on intravenous self-administration and rewarding properties of acute nicotine.

The effect of 7-week forced oral nicotine exposure on acquisition of intravenous nicotine self-administration, nicotine place conditioning, and nicotine preference was studied in mice. The nicotine solution was given in stepwise increased concentrations as the sole source of liquid for 7 weeks. Nicotine exposed animals self-administered nicotine intravenously at lower unit dose than nicotine-naïve ones, indicating that the forced 7-week nicotine exposure, followed by 7-day withdrawal, had rendered them more sensitive to nicotine's reinforcing effects.

Marinobufagenin (MBG) suppression of ethanol-seeking behavior is associated with inhibition of brain cortex Na/K-ATPase in mice.

In the present study the hypothesis was tested that sodium pump ligands (SPL) can modulate alcohol-seeking behavior and that this effect is related to changes in Na/K-ATPase activity in the central nervous system. Mice were tested for initiation of ethanol intravenous self-administration (IVSA) following i.p.

Endogenous digitalis-like ligands of the sodium pump: possible involvement in mood control and ethanol addiction.

This review addresses possible involvement of endogenous digitalis-like sodium pump ligands (SPL) in the mood control and ethanol addiction. Endogenous SPL include cardenolide and bufadienolide classes. Multiple SPL and multiple isoforms of the Na/K-ATPase, one of the key membrane enzymes, comprise a complex regulatory system.

[Effect of marinobufagenin on the primary reinforcing effect of ethanol].

Intraperitoneal administration of marinobufagenin resulted in a reliable and dose-dependent suppression of ethanol self-administration in drug- and experimentally naive DBA/2 mice. The findings suggest that Na/K-ATPase contributes to both mediation of the ethanol reinforcing properties and the mood regulation.

Analgesic effect of olipiphate on mouse model of chemical stimulation of peritoneum.

We studied the analgesic effect of olipiphate, a product of lignin, against writhing provoked by intraperitoneal injection of acetic acid. Paracetamol was used as the reference drug. Both agents dose-dependently decreased the number of motor reactions caused by the irritant.

Involvement of endogenous digitalis-like factors in voluntary selection of alcohol by rats.

This study tested the hypothesis that endogenous digitalis-like factor (DLF) is involved in the development of alcohol dependence in rats. In 33 male Wistar rats in conditioned place preference (CPP) experiment, ethanol evoked increase in time spent in the ethanol-associated compartment (702+/-82 in ethanol-treated vs. 426+/-86 sec in the controls).

Caffeine place conditioning in rats: comparison with cocaine and ethanol.

The present study employed the place conditioning technique to compare rewarding potential of caffeine with that of cocaine and ethanol. In Experiment 1 caffeine, cocaine and ethanol place conditioning were estimated independently, whereas in Experiments 2 and 3 the preference of the external cues associated with caffeine vs. cocaine and caffeine vs.

Opioid blockade attenuates acquisition and expression of cocaine-induced place preference conditioning in rats.

Endogenous opioid systems have been implicated in experimental cocaine addiction. One aspect of this involvement may be the modulation of the motivational properties of cocaine by endogenous opioids. The present study assessed the effect of opioid blockade with naloxone (NLX) on cocaine's motivational properties using the conditioned place preference procedure.

Analgesic and reinforcing effects of morphine in mice. Influence of Bay K-8644 and nimodipine.

The aim of the present work was to clarify the role of calcium influx through L-type calcium channels in the rewarding and analgesic effects of morphine. Therefore the effects of Bay K-8644 and nimodipine, dihydropyridine calcium agonist and antagonist, respectively, on the analgesic and rewarding effects of morphine in mice were studied. Morphine-induced analgesia was measured with the aid of writhing test, hot plate test and tail clip test.

Experimental estimation of addictive potential of a mixture of organic solvents.

In the present study we investigated in rats the reinforcing properties of glue vapours which are a mixture of four organic solvents (toluene 25%, benzine fraction 37%, ethyl acetate 31% and methylene chloride 7%). This mixture is used as a glue thinner and is a very popular among glue-sniffing children. Immediately after inhalation at a concentration of 7200 ppm, the glue vapours increased locomotor activity in the open field and response rate of self-stimulation in the lateral hypothalamus.

Isradipine is able to separate morphine-induced analgesia and place conditioning.

The effect of isradipine, a dihydropyridine calcium antagonist, on morphine-induced place preference and analgesia in rats and mice was studied. Isradipine (0.6-5.

[Neuroanatomical dissociation of reinforcing and analgetic effects of morphine].

Pain-relieving and reinforcing effects of morphine after microinjections into brain structures have been studied. Reinforcing effects were revealed after administration into n. accumbens, while analgesic--after injections into periventricular area of the midbrain and dorsomedial hypothalamus.

[The receptor organization of the reinforcing and analgetic opiate systems in the rat].

Comparative study of topographic and receptor selectivity of emotionally positive (place preference test) and analgetic (electrical and pressure nociceptive stimulation of the tail) effects of opioids was performed in rats. Morphine and selective agonists of mu-, kappa-, delta- and sigma-opiate receptors were administered through cannulae implanted into the periaqueductal grey and ventral tegmental area (VTA). Reinforcing effects of opioids in VTA was shown to be mediated mainly by mu-, delta- and sigma-receptors, while analgetic effect was realised with the aid of mu- and delta-opioid receptors.

[Positive reinforcing properties of klofelin].

The primary and secondary reinforcing and analgesic effects of clonidine were compared with those of morphine in the experiments on rats. Clonidine was demonstrated to possess weak positive reinforcing properties that make it possible to predict a relatively low narcogenic potential of this drug in comparison with morphine at the equianalgesic doses.

[Characteristics of opiate receptors in the brain and spinal cord of morphine tolerant mice].

The in vitro studies of 3H-morphine binding to synaptosomal brain and spinal cord membranes and the in vivo detection of pA2 values were carried out in mice. Both morphine-tolerant and intact animals were used. Morphine-tolerant mice showed no changes in specific binding and naloxone pA2 values.

[Reinforcing, but no analgesic, effect of opioid stimulation of the ventral tegmental area].

Analgesic and secondary reinforcing effects of morphine, bremazocine and phencyclidine microinjections into ventral tegmental area were studied in rats. The drugs under study failed to affect nociceptive reactions produced by thermal, mechanic and electrical stimuli. Morphine and phencyclidine have shown reinforcing properties in place preference paradigm.

[Characteristics of baroreceptor reflexes as affected by negative and positive emotions].

Changes of blood pressure (BP), intersystolic intervals (II), baroreflex sensitivity (BS) were studied during negative and positive emotions in unrestrained rats. Negative emotions induced raise of BP and reduced II and BS. The hemodynamic component of positive self-stimulation was due to its rewarding properties and not to direct effect of cerebral stimulation.

[Comparative characteristics of the discriminative and analgesic effects of morphine].

Experiments on mice were made to study and compare the discriminative and analgesic effects of morphine. The time-course of tolerance to the drug effects was found to be different. The Schild method permitted one to determine significantly different characteristics of naloxone antagonism (pA2) as regards the analgesic and discriminative effects of morphine.

[Effect of psychotropic agents on the manifestation of the morphine abstinence syndrome in mice].

Abstinence syndrome pattern produced by withdrawal of morphine injections in doses of 240 mg/kg daily was studied in experiments on mice. Pirroksan, butyroxan and carbidine (10 mg/kg intraperitoneally) inhibited manifestations of morphine withdrawal in an "open field" situation and depressed jumping activity. Phenazepam (20 mg/kg) depressed emotional hyperactivity in abstinent animals.

[Alteration of the hypothalamic electrical stimulation disconnection reaction in rats during chronic morphine administration].

Rats with electrodes implanted in the hypothalamus were trained to switch off the central stimulation. Animals were administered 12--30 injections of morphine in increasing doses (from 20 up to 120--180 mg/kg/injection). The drug exerted a dose-proportional suppressive effect on the escape response.

[Rat behavior in an "open field" when chronically administered morphine].

15-day long administration of morphine in doses of 20 to 120 mg/kg, injected twice daily produced initially a depression followed by an increased locomotor activity, more pronounced grooming behavior and less so--rearing. Abnormal forms of behavior like combined arrests and rapid movements, circling, stereatyped gnawing were also observed. Abstinence provoked by withdrawal of morphine or nalophine was characterized predominantly by the stimulation of locomotion and grooming with depressed rearing.