Biomedical subjects

J C Froehlich

Publications and source records attributed to J C Froehlich.

33 records · Page 2Linked to original sources

PubMed1995

The delta 2-opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference.

The relative importance of different opioid receptor types in mediating alcohol drinking behavior compared with the intake of other ingesta can be determined by characterizing the effects of selective opioid antagonists on the intake of various ingesta. Nonselective opioid receptor antagonists suppress the intake of many ingesta including alcohol, food, water, and sweets. Two distinct subtypes of delta-opioid receptors, delta 1 and delta 2, have recently been identified in rodent brain. We have previously reported that naltrindole (NTI), which blocks both delta 1 and delta 2 receptors, suppresses both alcohol and saccharin intake in rats selectively bred for high alcohol preference (P line). We now report that naltriben (NTB), an opioid antagonist that is selective for delta 2-opioid receptors, suppresses alcohol intake in rats of the P line and the effect appears to be both specific for alcohol and independent of alcohol palatability. NTB may reduce alcohol intake by attenuating the reinforcing pharmacological properties of alcohol.

Alcohol Deterrents↗

PubMed1995

Genetic factors in alcohol self-administration.

The realization that alcoholism is, in part, genetically determined has raised important questions regarding the nature of what is inherited when one inherits a predisposition toward high alcohol drinking. Rodent lines that have been selectively bred for high alcohol intake are excellent models of alcohol dependency. These animal models can be used to identify heritable biological characteristics that are associated with, and may be causally related to, high alcohol drinking and to investigate the efficacy of pharmacologic, environmental, and behavioral agents that have the potential to alter alcohol drinking behavior. In this paper, I review evidence that the endogenous opioid system plays an important role in mediating genetic differences in alcohol drinking behavior.

Adoption↗

PubMed1994

Opioid involvement in alcohol drinking.

A large body of evidence indicates that the endogenous opioid system plays an important role in maintaining alcohol drinking behavior. Evidence is reviewed that indicates that the reinforcing properties of alcohol that lead to continued and repeated bouts of drinking may be due, in part, to alcohol-induced activation of the endogenous opioid system. Much of this evidence is pharmacologic in nature. Blocking the action of endogenous opioid peptides via administration of opioid antagonists significantly attenuates alcohol consumption in animals under a variety of experimental conditions. In clinical trials, opioid receptor antagonists decrease alcohol consumption, relapse rates, subjective high, and alcohol craving in outpatient alcoholics. The potential clinical utility of opioid receptor antagonists in the treatment of alcoholism and alcohol dependence is discussed.

Alcohol Drinking↗

PubMed1993

Recent developments in alcoholism:opioid peptides.

A large body of evidence indicates that the endogenous opioid system plays an important role in maintaining alcohol drinking behavior. Research is reviewed indicating that the reinforcing properties of alcohol which lead to continued and repeated bouts of drinking are due, in part, to alcohol-induced activation of the endogenous opioid system. Opioid receptor antagonists decrease alcohol craving, alcohol consumption, and loss of control over drinking. The potential of opioid receptor antagonists to improve treatment outcome in comprehensive relapse prevention programs is discussed.

Alcohol Drinking↗

PubMed1992

Differences in the hypothermic response to ethanol in rats selectively bred for oral ethanol preference and nonpreference.

The duration of retention of tolerance to ethanol was tested in the alcohol-preferring (P) and alcohol-nonpreferring (NP) rats lines, using ethanol-induced hypothermia as a measure of tolerance. Rats received two injections of ethanol (3.5 g/kg) body wt, IP) and the time between the injections was 1, 2, or 3 days. When one day separated the two injections, tolerance to the hypothermic effect of a second "test" injection was found in both lines. When 2 or 3 days separated the two injections, the P line showed a loss of tolerance and the NP line showed sensitization to ethanol. Sensitization in the NP line grew stronger when the interval between injections was increased from 2 to 3 days. The duration of retention of tolerance to ethanol-induced hypothermia in the P line was shorter than has previously been reported for motor impairment in this line. It appears that the duration of tolerance retention in the P line depends on the test used to measure tolerance. Sensitization to ethanol in the NP line may be associated with low oral ethanol intake.

Alcohol Drinking↗

PubMed1991

Importance of delta opioid receptors in maintaining high alcohol drinking.

We have previously reported that naloxone, a nonspecific opioid receptor antagonist, suppresses alcohol but not water consumption by male rats that have been genetically selected for high voluntary alcohol drinking. However, the identity of the specific opioid receptor subtype that may mediate alcohol drinking is not known. This paper reports that a selective delta opioid receptor antagonist is as effective as naloxone in suppressing alcohol consumption and that an enkephalinase inhibitor, which potentiates the action of endogenous enkephalins, increases alcohol intake. These results suggest that alcohol-induced activation of the endogenous enkephalinergic system, and occupation of delta opioid receptors, are involved in the maintenance of continued alcohol drinking.

Alcohol Drinking↗

PubMed1991

Animal models for the study of alcoholism: utility of selected lines.

One recent advance in the field of alcohol research has been the recognition that a predisposition to develop alcoholism is, in part, genetically determined. It now remains to identify the factors, which, when inherited, increase risk for alcoholism. One approach to this problem is to analyze how organisms with identifiable genetic predisposition towards ethanol drinking differ from organisms without genetic risk. Such an approach may lead to the identification of neurochemical, neurophysiological or neuroanatomical factors which, when inherited alone, or in combination, serve to predispose an organism towards ethanol drinking.

Alcohol Drinking↗

PubMed1990

Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference.

The effect of naloxone on voluntary ethanol intake was examined in rats which were selectively bred for oral ethanol preference (High Alcohol Drinking or HAD line). Rats of the HAD line were treated with naloxone in doses of 0.05-18.0 mg/kg b.wt. before access to water alone or to a free-choice between a 10% (v/v) ethanol solution and water. Naloxone suppressed water intake when water was presented as the sole source of fluid. In contrast, naloxone produced a dose-dependent decrease in ethanol consumption, without altering water intake, when rats were given a free-choice between the ethanol solution and water. Selective suppression of ethanol consumption by naloxone was not attributable to changes in blood ethanol concentrations or ethanol elimination rates following naloxone treatment. It appears that although naloxone may attenuate the positively reinforcing properties of both ethanol and water, ethanol drinking is a subset of consummatory behaviors that is particularly sensitive to opioid receptor blockade. The results suggest that activation of the endogenous opioid system may be an important mechanism which serves to maintain continued ethanol drinking.

Alcohol Drinking↗

PubMed1988

Differences in response to the aversive properties of ethanol in rats selectively bred for oral ethanol preference.

A conditioned taste aversion (CTA) paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to genetic differences in voluntary ethanol consumption. Four doses of ethanol, administered IP, were paired with the consumption of a 0.1% saccharin solution in rats from the alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Repeated pairing of saccharin and ethanol in a dose of 1.0 g/kg produced stronger and more prolonged aversion to saccharin in NP rats, compared with P rats, at comparable blood ethanol levels. A low dose of ethanol (0.25 g/kg) produced transient conditioned facilitation of saccharin consumption in P rats, but not in NP rats, at comparable blood ethanol levels. The results suggest that rats of the NP line find the postingestional effects of high-dose ethanol more aversive, and low-dose ethanol less reinforcing, than do rats of the P line. Genetic differences in voluntary ethanol consumption may be due, in part, to differences in aversion to the postingestional effects of ethanol.

Alcohol Drinking↗

PubMed1988

Pharmacology of alcohol preference in rodents.

In alcoholism research, two fundamental and closely related questions are: "Why do people drink?" and "Why do some people drink too much?" Humans voluntarily drink alcoholic beverages or self-administer alcohol, more often than not, in a social setting. Environmental factors and how individuals react to them can, therefore, have powerful influences on drinking behavior. On the other hand, the neuropsychopharmacological actions of ethanol and how different individuals react to them can be important biological determinants. Ethanol's action is biphasic, i.e., it can be reinforcing (rewarding) in the low concentration range, but aversive at high concentrations. Perception by the individual of the reinforcing actions of ethanol might be expected to maintain alcohol-seeking behavior, whereas aversive effects would be expected to extinguish this behavior. Identification of the environmental and biological variables that promote and maintain alcohol-seeking or alcohol self-administration behavior is key to our understanding of the disorder alcoholism itself.

Alcoholism↗

PubMed1987

Naloxone attenuation of voluntary alcohol consumption.

The effect of naloxone on voluntary alcohol consumption was examined in two lines of rats which have recently been selectively bred for oral alcohol preference (High Alcohol Drinking or HAD line) or aversion (Low Alcohol Drinking or LAD line). Genetic differences in brain met-enkephalin content were examined in two additional lines of rats which have been genetically selected for oral alcohol preference (Alcohol-Preferring or P line) or aversion (Alcohol-Nonpreferring or NP line).

Alcohol Drinking↗

PubMed1985

Interaction between the posterior pituitary and LHRH in the control of LH secretion.

We have recently reported that the posterior lobe of the pituitary differentially inhibits the secretion of prolactin (PRL) and luteinizing hormone (LH), but not follicle stimulating hormone (FSH) throughout the estrous cycle. Removal of the posterior pituitary (posterior pituitary lobectomy) results in elevations of plasma LH on all days of the cycle except on diestrus-day-2. In the present study we examined: whether the control of LH release involves an interaction between the posterior pituitary and hypothalamic luteinizing hormone-releasing hormone (LHRH), and whether the elevation of LH seen following posterior lobectomy is due to the removal of a posterior pituitary substance(s) which alters anterior pituitary sensitivity to LHRH. In order to block the action of hypothalamic LHRH, a potent LHRH inhibitory analog (50 micrograms) was injected SC two hours prior to removal of the posterior pituitary in estrous rats. Administration of the inhibitory analog completely eliminated the elevation of plasma LH seen following posterior lobectomy, but did not alter the posterior lobectomy-induced rise of plasma PRL, or plasma FSH concentrations. In order to test whether anterior pituitary sensitivity to LHRH is altered by posterior lobectomy, a moderate dose of LHRH (15 ng) was administered to both posterior lobectomized and sham lobectomized estrous rats. The time-course and magnitude of the LH response to LHRH was similar in both groups. The results are consistent with the hypothesis that LH secretion is controlled by an interaction between hypothalamic LHRH and the posterior lobe of the pituitary, but this interaction does not appear to involve lobectomy-induced changes in anterior pituitary responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Genetic differences in avoidance learning by Rattus norvegicus: escape/avoidance responding, sensitivity to electric shock, discrimination learning, and open-field behavior.

The behaviors of rats selectively bred for either good or poor shuttle box avoidance learning were studied. The results of Experiment 1 indicated that the phenotypic difference in avoidance learning is not associated with differences in speed of escape or avoidance responding. Differences between the lines in frequency of intertrial responses (ITRs), which appear during training but not during pretest, suggest that ITRs in animals of the low-avoidance (SLA) line are more suppressed by electric shock than in animals of the high-avoidance (SHA) line. This result suggests that SLA animals may be more emotionally responsive than SHA animals. Experiment 2 demonstrated that the animals of the two lines do not differ in absolute sensitivity to electric shock, and Experiment 3 showed that the poor performance of the SLA line is not due to an inability to learn. Experiment 3 also provided evidence which suggests that the poor avoidance learning by SLA animals is due to their emotional reactivity. Observations of open-field behavior in Experiment 4 are consistent with this hypothesis. The major consistent correlate of the phenotypic difference in avoidance learning is greater emotionality or emotional reactivity in SLA than in SHA animals.

Animals↗

PubMed1984

Posterior pituitary involvement in the control of luteinizing hormone and prolactin secretion during the estrous cycle.

The effects of removal of the posterior lobe of the pituitary on plasma concentrations of PRL, LH, and FSH were examined under the following conditions: on each morning of the 4-day estrous cycle, 2 weeks after ovariectomy, and 2 h after the administration of a LHRH inhibitory analog on estrus. Blood was collected from a femoral artery immediately before and during the 3 h after posterior pituitary lobectomy or sham lobectomy. Significant elevations of both PRL and LH were seen after removal of the posterior pituitary on estrus and diestrus day 1, while no change was seen in the plasma concentration of either hormone after posterior pituitary removal on diestrus day 2. On proestrus, posterior lobectomy resulted in an elevation of LH only. The posterior lobectomy-induced PRL elevations were rapid and of short duration, while those of LH were delayed and prolonged. No alteration in plasma FSH concentrations was seen after posterior pituitary lobectomy performed on any day of the estrous cycle. In contrast to the hormonal elevations observed after lobectomy during the cycle, no change in plasma PRL, LH, or FSH was seen after posterior lobectomy in ovariectomized rats. The administration of a LHRH inhibitory analog 2 h before posterior lobectomy completely abolished the lobectomy-induced rise of LH normally seen on estrus. The data suggest that the posterior pituitary participates in the regulation of PRL and LH, but not FSH, release during the estrous cycle. Given that the posterior lobectomy-induced elevations of plasma PRL and LH were evident only on certain days of the cycle and were absent in ovariectomized rats, it is likely that posterior pituitary inhibition of PRL and LH release is expressed only in the presence of specific ovarian hormonal profiles. In addition, the posterior lobectomy-induced rise in plasma LH appears to be dependent on the presence of LHRH, but it remains to be determined whether a posterior pituitary substance(s) alters hypothalamic release of or anterior pituitary responsiveness to LHRH.

Animals↗

PubMed1979

Genetic selection for avoidance behavior in the rat.

Long-Evans rats were selectively bred for over 20 generations using two behavioral criteria: (1) limited responding to the warning signal during ten pretest trials and (2) either good or poor avoidance behavior during 60 avoidance training trials in a two-way shuttlebox. The results suggest that avoidance behavior in the rat is a heritable characteristic that may be selected independently of activity level.

Animals↗