Rats orally self-administer corticosterone

doi:10.1016/0006-8993(93)90837-D

Brain Research

Volume 622, Issues 1–2, 17 September 1993, Pages 315-320

https://doi.org/10.1016/0006-8993(93)90837-D Get rights and content

Abstract

Corticosterone, the major glucocorticoid in the rat, may modulate the reinforcing properties of addictive drugs as well as act as a positive reinforcer for intravenous self-administration. Since glucocorticoids are generally administered to humans via the oral route, we examined the ability of corticosterone to induce oral self-administration in the rat. In a first experiment, animals with free access to food could choose between a corticosterone solution and water. Three doses (25, 50 and 100 μg/ml) were tested. The group receiving the 100 μg/ml dose was also submitted to an extinction followed by a reversal test. In a second experiment, we examined whether the reinforcing properties of corticosterone could induced drinking independently of food intake. In the pre-test phase rats had access to food only during a fixed period of the day (11.00 h to 14.00 h). Corticosterone solution (200 μg/ml) or tap water were available during this period, with free access to tap water for the rest of the day. During the test period, access to food was shifted forward in time, while the availability of the corticosterone solution remained the same. The first experiment showed that rats preferred a corticosterone solution to tap water, developing self-administration in a dose-dependent manner. This preference could be extinguished, but was regained during the reversal phase. In the second experiment, animals that had access to the corticosterone solution drank more than rats that had access to water in the absence of food. These results indicate that corticosterone has reinforcing properties after oral administration. Furthermore, they suggest that corticosterone may exert its effects on the reinforcing properties of addictive drugs by a direct action on reinforcement systems. This could account for some of the side effects of chronic steroid treatment.

Reference (39)

CarrollM.E.
Rapid acquisition of oral phencyclidine self-administration in food-deprived and food-satiated rhesus monkeys: concurrent phencyclidine and water choice
Pharmacol. Biochem. Behav.
(1982)
ChaoH.M. et al.
Glucocorticoid regulation of neuropeptide mRNAs in the rat striatum
Mol. Brain Res.
(1991)
De KloetE.R. et al.
Decreased serotonin turnover in the dorsal hippocampus of the rat brain shortly after adrenalectomy: selective normalization after corticosterone substitution
Brain Res.
(1982)
DerocheV. et al.
Repeated corticisterone administration sensitizes the locomotor response to amphetamine
Brain Res.
(1992)
DickinsonS.L. et al.
Reduced 5-hydroxytryptamine-dependent behaviour in rats following chronic corticosterone treatment
Brain Res.
(1985)
DixonR.B. et al.
On the various forms of corticosteroid withdrawal syndrome
Am. J. Med.
(1980)
PiazzaP.V. et al.
Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration
Brain Res.
(1990)
SapolskyR.M.
Glucocorticoids, hippocampal damage and the glutamatergic synapse
Prog. Brain Res.
(1990)
AkanaS.F. et al.
Corticosterone: narrow range required for normal body and thymus weight and ACTH
Am. J. Physiol.
(1985)
AntelmanS.M.
Stressor-induced sensitization to subsequent stress: implications for the development and treatment of clinical disorders

BadianiA. et al.

The kappa-opioid U-50,488H suppresses the initiation of nocturnal spontaneous drinking in normally hydrated rats

Psychopharmacology

(1992)

BormannJ. et al.

Gamma-amino-butyric acid receptor channels in adrenal chromaffin cells: a patch-clamp study

ChaoH.M. et al.

Glucocorticoid regulation of preproenkephalin messenger ribonucleic acid in the rat striatum

Endocrinology

(1990)

HallE.D. et al.

Effects of single intravenous glucocorticoid dose on biogenic amine levels in cat lumbar spinal cord

J. Neurochem.

(1982)

Ha¨rfstrandA. et al.

Glucocorticoid receptor immunoreactivity in monoaminergic neurons in the rat brain

HenningfieldJ.E. et al.

Establishment of orally delivered ethanol as a positive reinforcer for rhesus monkeys

HolsboerF.

Psychiatric implications of altered limbic-hypothalamic-pituitary-adrenocortical activity

Eur. Arch. Psychiatr. Neurol. Sci.

(1989)

KennedyJ.A. et al.

Metyrapone-induced withdrawal symptoms

Br. J. Addict.

(1990)

KoobG.F. et al.

Cellular and molecular mechanisms of drug dependence

Science

(1989)

Cited by (96)

Changes in maternal fecal corticosterone metabolites across lactation and in response to chronic stress
2021, General and Comparative Endocrinology
Maternal exposure to stressors during lactation has previously been demonstrated to impact various aspects of milk synthesis and to have long-term physiological effects on offspring. Much of the current literature investigating the effects of stress during lactation has used acute stressors, and the studies investigating the effects of chronic stressors largely focus on neurological changes. Further, temporal variation in glucocorticoids across lactation in response to stressors has rarely been assessed. The present work uses a novel male intruder paradigm to model the effects of chronic stress on maternal fecal corticosterone metabolites (FCMs) in Sprague-Dawley rats across lactation. FCM levels were elevated in chronically-stressed mothers relative to the control group. Further, FCMs in the stress group were time-dependent either due to repeated exposure to the stressor or lactation stage. Together, this work demonstrates the efficacy of this established paradigm in increasing circulating glucocorticoids in lactating rats. These results highlight the need for repeated temporal sampling, as glucocorticoid levels in response to a chronic stressor may change across lactation.
The ergogenic impact of the glucocorticoid prednisolone does not translate into increased running motivation in mice
2020, Psychoneuroendocrinology
Glucocorticoids, such as prednisolone, are considered sport doping agents owing to their ergogenic properties. These are accounted for by peripheral mechanisms associated with energetic and anti-inflammatory processes. However, because glucocorticoids target brain tissues, it is likely that these ergogenic impacts are associated with central effects. One of these might be reward motivation, which relies on glucocorticoid receptor-expressing mesocorticolimbic dopaminergic neurons. In keeping with this possibility, this study has explored in mice whether repeated prednisolone administration (5 or 15 μg/ml of drinking water for 10 days) affected intrinsic motivation for running, a strong reinforcer in rodents. Running motivation was assessed by means of a cued-reward motivated instrumental task wherein wheel-running was conditioned by prior nose poke responses under fixed (FR), and then progressive (PR), ratio reinforcement schedules. Sub-chronic ingestion of prednisolone decreased the running distance covered during each rewarded sequence under FR schedules. This finding did not extend to wheel-running performances in mice provided free (i.e. unconditioned) wheel-running opportunities. Running motivation, as estimated under a PR reinforcement schedule, was found to be decreased (lowest concentration) or to remain unaffected (highest concentration) by prednisolone concentration. Lastly, an inter-individual analysis of the respective effects of prednisolone on muscular endurance (as assessed in the wire grid-hanging test) and on running motivation indicated that the former was not predictive of the latter. This observation suggests that prednisolone ergogenic impacts might occur without any concomitant increase in intrinsic exercise motivation.
Endocrine Regulations in Human–Dog Coexistence through Domestication
2019, Trends in Endocrinology and Metabolism
Endocrine system regulation is important for the maintenance of homeostasis; it controls hormonal functions in complex physiology and behavior and adaptations to social environments. Evidence indicates that for more than 35 000 years, dogs (Canis familiaris) have been domesticated through living with humans. For example, they have acquired human-like social skills, such as eye gazing and pointing gestures. These unique behaviors are, at least partially, regulated by hormones and are thought to have been genetically altered throughout domestication. Glucocorticoids affect social tolerance, while oxytocin facilitates social coordination and familiarity between individuals. We review historical and recent literature to facilitate an understanding of the roles of glucocorticoid and oxytocin functions in the human–canine coexistence dynamic established during domestication.
Addiction and stress: An allostatic view
2019, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Reward and stress represent different components of transitions in our brain emotional systems that lead to and perpetuate addiction. For example, many studies demonstrate that rats with higher levels of corticosterone and CRF are more likely to self-administer cocaine, heroin, and amphetamines (Piazza et al., 1989, 1993; Erb et al., 1996), and corticosterone is self-administered by rats (Deroche et al., 1993; Piazza et al., 1993; Fig. 2). Thus, an early allostatic change occurs in the activity of elements of the reward system to facilitate the function of the mesolimbic dopamine incentive salience system and promote excessive drug seeking.
Allostasis, or stability through change, has most often been linked with challenges to homeostasis, in which repeated challenges or stressors produce sufficient allostatic load to generate an allostatic state that can ultimately lead to a disease state. The present review argues that the impact of stress on drug addiction fits with an allostatic model and represents a challenge to brain circuit regulatory mechanisms that underlie the emotional state of the animal. The central thesis is that stress leads to changes in corticotropin-releasing factor in the brain that impact addiction. Stress is further argued to impact all three stages of the addiction cycle—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—exposing the animal to an emotional allostatic load and allostatic state that forms the growing motivational pathology of addiction. Viewing addiction as an allostatic mechanism provides key insights into the ways in which dysregulated neurocircuitry that is involved in basic motivational systems can transition to pathophysiology.
Influence of corticosterone on growth, home-cage activity, wheel running, and aerobic capacity in house mice selectively bred for high voluntary wheel-running behavior
2019, Physiology and Behavior
Glucocorticoids, a class of metabolic hormones, impact a wide range of traits (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and variation in concentrations of circulating glucocorticoids (such as corticosterone), at the level of natural individual variation, in relation to endocrine disorders, or from exogenous supplementation, have manifold effects. Changes in circulating corticosterone concentrations can also impact multiple aspects of locomotor behavior, including both motivation and physical ability for exercise. To examine further the role of corticosterone in locomotor behavior and associated traits, we utilized laboratory house mice from a long-term experiment that selectively breeds for high levels of voluntary exercise. As compared with four non-selected control (C) lines, mice from the four replicate High Runner (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations as well as ~3-fold higher voluntary wheel running on a daily basis, higher home-cage activity when deprived of wheels, higher maximal aerobic capacity, and smaller body size; potentially, all of these differences could be modulated by circulating corticosterone. We administered 50 μg/mL corticosterone-21-hemisuccinate in the drinking water of both HR and C male mice from weaning through ~8 weeks of age. As compared with mice from C lines, HR mice had higher endogenous corticosterone levels; higher daily wheel-running distance, duration, and speed; higher maximal oxygen consumption during forced exercise (VO₂max); spent more time in the closed arms of an elevated plus maze; and had larger reproductive fat pads. For both HR and C mice, corticosterone treatment strongly suppressed endogenous circulating corticosterone levels, decreased growth rate and adult body mass, increased food and water consumption (both adjusted for body mass), increased entries into closed arms of an elevated plus maze, decreased home-cage activity (total and average intensity), decreased wheel-running distance and maximum speed, and decreased VO₂max. At the suborganismal level, corticosterone treatment decreased relative adrenal, liver, and triceps surae muscle mass, as well as tail length, but increased both subdermal and reproductive fat pad masses, as well as hematocrit. Overall, the responses of both HR and C mice to corticosterone supplementation were “negative” from a health perspective. These results have significant implications for understanding both the evolution of baseline corticosterone levels and stress-related effects on activity levels. They also suggest that patients experiencing extended periods of glucocorticoid treatment might benefit from attempts to increase their physical activity as an adjuvant.
Modified single prolonged stress reduces cocaine self-administration during acquisition regardless of rearing environment
2018, Behavioural Brain Research
Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in cocaine self-administration and HPA markers. Regardless of rearing condition, rats exposed to modSPS had greater corticosterone (CORT) release and reduced cocaine self-administration during initial acquisition compared to non-stressed controls. In addition, during initial acquisition, rats that received both Iso rearing and modSPS showed a more rapid increase in cocaine self-administration across sessions compared to Enr and Std rats exposed to modSPS. Following initial acquisition, a dose response analysis showed that Iso rats were overall most sensitive to changes in cocaine unit dose; however, modSPS had no effect on the cocaine dose response curve. Further, there was no effect of either modSPS or differential rearing on expression of glucocorticoid receptor (GR) in hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using modSPS in combination with Iso housing, this study identified unique contributions of each stressor to acquisition of cocaine self-administration.

View all citing articles on Scopus

View full text

Rats orally self-administer corticosterone

Abstract

Pharmacol. Biochem. Behav.

Mol. Brain Res.

Brain Res.

Brain Res.

Brain Res.

Am. J. Med.

Brain Res.

Prog. Brain Res.

Corticosterone: narrow range required for normal body and thymus weight and ACTH

Am. J. Physiol.

Stressor-induced sensitization to subsequent stress: implications for the development and treatment of clinical disorders

The kappa-opioid U-50,488H suppresses the initiation of nocturnal spontaneous drinking in normally hydrated rats

Psychopharmacology

Gamma-amino-butyric acid receptor channels in adrenal chromaffin cells: a patch-clamp study

Glucocorticoid regulation of preproenkephalin messenger ribonucleic acid in the rat striatum

Endocrinology

Effects of single intravenous glucocorticoid dose on biogenic amine levels in cat lumbar spinal cord

J. Neurochem.

Glucocorticoid receptor immunoreactivity in monoaminergic neurons in the rat brain

Establishment of orally delivered ethanol as a positive reinforcer for rhesus monkeys

Psychiatric implications of altered limbic-hypothalamic-pituitary-adrenocortical activity

Eur. Arch. Psychiatr. Neurol. Sci.

Metyrapone-induced withdrawal symptoms

Br. J. Addict.

Cellular and molecular mechanisms of drug dependence

Science