The Influence of Cross-Fostering on Alcohol Consumption and Depressive-Like Behaviors in HA and LA Mice: The Role of the Endogenous Opioid System.

The development of alcohol dependence and depression is determined by various genetic and environmental factors. In the presented study, we used high analgesia (HA) and low analgesia (LA) mouse lines, characterized by different endogenous opioid system activity and divergent blood-brain barrier permeability, to determine the influence of cross-fostering of these lines raised by surrogate mothers on ethanol consumption and development of depressive-like behaviors. We also investigated ethanol drinking by biological parents or surrogate mothers.

Differential role of specific cardiovascular neuropeptides in pain regulation: Relevance to cardiovascular diseases.

In many instances, the perception of pain is disproportionate to the strength of the algesic stimulus. Excessive or inadequate pain sensation is frequently observed in cardiovascular diseases, especially in coronary ischemia. The mechanisms responsible for individual differences in the perception of cardiovascular pain are not well recognized.

Delta-opioid receptor antagonism leads to excessive ethanol consumption in mice with enhanced activity of the endogenous opioid system.

The opioid system modulates the central reinforcing effects of ethanol and participates in the etiology of addiction. However, the pharmacotherapy of ethanol dependence targeted on the opioid system is little effective and varies due to individual patients' sensitivity. In the present study, we used two mouse lines with high (HA) and low (LA) activity of the endogenous opioid system to analyze the effect of opioid receptor blockade on ethanol drinking behavior.

Association between the A107V substitution in the δ-opioid receptors and ethanol drinking in mice selected for high and low analgesia.

Experimental evidence suggests that endogenous opioids play an important role in the development of ethanol addiction. In this study, we employed two mouse lines divergently bred for opioid-mediated stress-induced analgesia. In comparison with HA (high analgesia line) mice, LA (low analgesia line) mice, having lower opioid receptor system activity, manifest enhanced basal as well as stress-induced ethanol drinking.

Distinct susceptibility to inoculated melanoma and sensitivity to cancer pain in mouse lines with high and low sensitivity to stress.

Approximately 30 years ago, we developed 2 mouse lines with enhanced and decreased opioid system activity using bidirectional selection for high (high analgesia [HA] line) and low (low analgesia [LA] line) swim stress-induced analgesia. These mouse lines differ substantially in pain sensitivity, measured as hind paw withdrawal latency in a hot plate test. Moreover, compared with the LA mice, the HA mice exhibited reduced energy expenditure under stress and different depression-like behavior as well as higher sensitivity to mutagens and the high frequency of spontaneous and carcinogen-induced tumors.

Differential startle magnitude in mice selected for high and low swim analgesia is not related to difference in nociception.

The acoustic startle response (ASR) elicited by 110 dB 10-ms pulses was studied in relation to pain sensitivity in mouse lines selectively bred for high (HA) and for low (LA) swim analgesia. The magnitudes of ASR, similarly as hot-plate latencies, differed between the lines in the rank order HA is greater than unselected controls (C) greater than LA. The animals' nociception did not change after the ASR session consisting of a sequence of 20 acoustic stimuli.

Acoustic startle and disruption of prepulse inhibition by dizocilpine in selectively bred mice.

In this study we examined the relationship between genetically produced differences in the magnitude of prepulse inhibition (PPI) of the acoustic startle response (ASR) and stress induced swim analgesia in genetically different strains of mice. Prepulse inhibition of the ASR and its changes due to dizocilpine (MK-801) injection were studied in 180 mice. The animals used in this study were obtained from our colony of 54 generation, Swiss-Webster mice selectively bred for high and low magnitude of analgesia.

A polymorphism in exon 2 of the delta-opioid receptor affects nociception in response to specific agonists and antagonists in mice selectively bred for high and low analgesia.

This study searched for polymorphic sites in the murine mu-, delta- and kappa-opioid receptors that presumably influence pain perception. We employed two mouse lines divergently bred for high (HA, high analgesia line) and low (LA, low analgesia line) swim stress-induced analgesia (SSIA). These mouse lines differ substantially in pain sensitivity, measured as hind paw withdrawal latency in the hot-plate test.

Opposite effects of alcohol in regulating stress-induced changes in body weight between the two mouse lines with enhanced or low opioid system activity.

Considering the involvement of the opioid system in alcoholism, depression and metabolism - known risk factors in human obesity, we studied the effects of chronic mild stress (CMS) and alcohol intake on body weight in two mouse lines selected for high (HA-high analgesia) or low (LA-low analgesia) swim stress-induced analgesia. In comparison to LA mice, HA mice exhibit an upregulation of opioid receptor system function, different depression-like behavior and reduced energy expenditure in stress. LA animals showed enhanced basal and CMS-induced alcohol drinking versus HA.

Alcohol reverses depressive and pronociceptive effects of chronic stress in mice with enhanced activity of the opioid system.

The role of the opioid system in mediating effects of alcoholism and stress in depression is far from clear. We studied, therefore, the effects of chronic mild stress (CMS) and alcohol drinking on depression-like behavior and nociception in lines of mice selected for high (HA) or low (LA) swim stress-induced analgesia. Compared to the LA mice, the HA animals display up-regulation of opioid receptor system function and depression-like behavior in tail suspension test (TST).

Differences in ethanol drinking between mice selected for high and low swim stress-induced analgesia.

Alcoholism is a complex disorder, still not fully understood, in which environmental and inherited risk factors play essential roles. Of particular importance may be chronic exposure to stress thought to increase preference for ethanol in genetically susceptible individuals. Animal and human data suggest that the opioid system may be involved in the development of alcohol dependence.

Lipopolysaccharide does not affect acoustic startle reflex in mice.

Bacterial endotoxin (lipopolysaccharide; LPS) evokes in rodents an adaptive sickness behavior. It also produces changes in stress hormones secretion and activity of brain serotonergic and noradrenergic systems that have been implicated in stress responses, fear, and anxiety. Acoustic startle reflex (ASR) is regarded as a protective behavioral response that is enhanced in threatening situations or following an aversive event, and it can be modulated by physiological and emotional state of an animal.

[Lactoferrin in the central nervous system].

Lactoferrin (LF) is a protein secreted by the tissues of ectodermal origin. Its structure is similar to transferrin. LF appeared to be multifunctional, but its main functions are connected with the natural defense system of mammals.

Chromosomal NOR activity in mice selected for high and low swim stress-induced analgesia.

Metaphase nucleolar organizer region (NOR) activity was studied in mouse lines selectively bred for high analgesia (HA) and for low analgesia (LA) induced by 3-min swimming in 20 degrees C water. Apart from pain-related traits, HA mice also manifest, as compared to the LA line, higher emotionality in certain behavioral tests and are less capable of coping with the hypothermic challenge of swimming in cold water, in addition to being more susceptible to the mutagenic effect of whole-body gamma-radiation and mitomycin C injection. We here compared NOR activity in HA and LA mice.

Analgesia induced by swim stress: interaction between analgesic and thermoregulatory mechanisms.

Exposure of an animal to stressful stimuli, perceived by the animal as a threatening, emergency condition, elicits a transient decrease of pain sensitivity, which often affects thermoregulatory mechanisms in the threatened organism. We studied the interaction between emergency and thermoregulatory components of swim stress in developing swim stress-induced analgesia (SSIA). The subjects were mice selectively bred for high analgesia (HA) induced by swimming in 20 degrees C water, and displaying profound swim hypothermia.

Effect of cold acclimation and repeated swimming on opioid and nonopioid swim stress-induced analgesia in selectively bred mice.

Swiss-Webster mice selectively bred for high swim stress-induced analgesia (SSIA) were exposed to continuous ambient cold (5 degrees C) for 6 weeks or to daily 3-min swims for 14 consecutive days either in 20 or 32 degrees C water. Thereafter, mice subjected to the particular procedure were injected intraperitoneally with 10 mg/kg of naltrexone HCl and were tested for modification of the opioid and nonopioid component of SSIA. SSIA was reduced following swims at either water temperature and was antagonized by naltrexone to greater extent than in nonswimming mice.

Cytogenetic comparison of the sensitivity to mutagens in mice selected for high (HA) and low (LA) swim stress-induced analgesia.

Sensitivity to mutagens was studied in mouse lines selectively bred for high analgesia (HA) and for low analgesia (LA) induced by 3-min swimming in 20 degrees C water. Apart from pain-related traits HA mice also manifest, as compared to the LA line, higher emotionality in various behavioural tests, and cope worse with the hypothermic challenge of swimming in cold water. In the present study HA mice appeared more susceptible to the mutagenic effect of whole-body gamma-radiation and mitomycin-C injection.

Differential metabolic capacity of mice selected for magnitude of swim stress-induced analgesia.

Maximum oxygen consumption (Vo(2)) elicited by swimming in 20 degrees C water or by exposure to -2.5 degrees C in helium-oxygen (Helox) atmosphere is higher in mice selected for low (LA) than for high (HA) stress-induced analgesia (SIA) produced by swimming. However, this line difference is greater with respect to swim- than to cold-elicited Vo(2).

One or two genetic loci mediate high opiate analgesia in selectively bred mice.

The analgesic responses of humans and laboratory animals are characterized by substantial individual differences. The genetic basis of this variability can be studied experimentally in rodents using a program of selective breeding. One such program selected for high (HA) and low (LA) swim stress-induced analgesia (SSIA) on the hot-plate (56 degrees C) test in Swiss-Webster mice.