PubMed Health⌕ Search

Biomedical subjects

C L Broekkamp

Publications and source records attributed to C L Broekkamp.

At least 19 recordsLinked to original sources
PubMed1999

Antagonism of the 5-HT1A receptor stimulus in a conditioned taste aversion procedure.

The conditioned taste aversion procedure in mice was used to test for blockade of the drug stimulus of the 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT), 1-(4-trifluoromethyl-2-pyridinyl)-4- [4-[2-oxo-1-pyrrolidinyl]butyl]piperazine (E)-2-butenedioate (Org 13011) and the 5-HT reuptake inhibitor fluoxetine. The conditioned taste aversion induced by 8-OH-DPAT (0.22 mg/kg) and Org 13011 (0.5 mg/kg) was readily blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY-100635) (0.1 mg/kg). The conditioned taste aversion induced by fluoxetine could not be antagonized by WAY-100635 nor by the 5-HT2 receptor antagonist mianserin. It is concluded that the conditioned taste aversion induced by 8-OH-DPAT or Org 13011 is mediated via 5-HT1A receptors. The results suggest that the conditioned taste aversion induced by fluoxetine is not exclusively mediated by 5-HT1A receptors nor exclusively by 5-HT2 receptors. The results also indicate that the conditioned taste aversion paradigm can be used to test for antagonism of stimulus properties of compounds.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats.

Activation of 5-HT1A receptors has been shown to attenuate catalepsy induced by typical antipsychotic compounds. Since mirtazapine (Remeron; Org 3770) has indirect 5-HT1A receptor stimulating properties as well as antagonist properties at alpha2-adrenoceptors and 5-HT2 receptors, it was of interest to investigate how the compound could modulate the effect of haloperidol on apomorphine-induced climbing behaviour in mice and haloperidol-induced catalepsy in rats. In the apomorphine climbing test, it was found that mirtazapine (2.2-22 mg/kg) did not change the climbing behaviour of mice induced by 1 mg/kg of apomorphine. However, when given as a co-treatment with haloperidol, mirtazapine (1 and 10 mg/kg) dose-dependently augmented the inhibiting effect of haloperidol on this climbing behaviour. Co-treatment with the 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) also augmented the effect of haloperidol. Catalepsy induced by haloperidol (4.6 mg/kg) was attenuated by mirtazapine (2.2-22 mg/kg). The strongest effect was seen at 90 min after haloperidol treatment. The results obtained in these experiments suggest that co-treatment with mirtazapine may enhance the antipsychotic effect of haloperidol and reduce its extrapyramidal side effects, thereby widening its therapeutic window.

Animals↗
PubMed1998

Stimulus properties of fluvoxamine in a conditioned taste aversion procedure.

A conditioned taste aversion (CTA) procedure in mice was used to investigate the stimulus effects of the serotonin reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine. Fluvoxamine elicited a reliable CTA (ED50 = 24 mg/kg, SC) and a number of drugs were tested as pre-exposure drugs. Pre-exposure to the serotonin (5-HT)1A receptor agonists flesinoxan and +/- -8-hydroxy-dipropylaminotetralin (8-OH-DPAT) prevented the CTA induced by fluvoxamine (50 mg/kg, SC). Pre-exposure with the 5-HT2C receptor agonist MK 212 [6-chloro-2(1-piperazinyl)pyrazine] partially prevented the fluvoxamine-induced CTA, pre-exposure with the 5-HT2A/2C receptor agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] did not prevent the CTA induced by fluvoxamine. Flesinoxan pre-exposure also prevented the taste aversion induced by fluoxetine (10 mg/kg, SC) completely. This contrasts previous results obtained with fluoxetine, where was found that its stimulus is primarily mediated by 5-HT2C, and to a lesser degree by 5-HT1A receptors. Therefore, we compared the two SSRIs directly. Pre-exposure to fluvoxamine prevented the fluoxetine-induced CTA, whereas pre-exposure to fluoxetine only partially prevented the fluvoxamine-induced CTA. We conclude that 5-HT1A receptors are involved in the stimulus properties of both fluvoxamine and fluoxetine, that 5-HT2C receptors are involved in fluvoxamine and especially fluoxetine, and, based primarily on the cross-comparison tests, that the two SSRIs have somewhat different stimulus properties.

Animals↗
PubMed1998

Antiaversive effects of 5HT2C receptor agonists and fluoxetine in a model of panic-like anxiety in rats.

Dose-dependent increases in threshold for operant fear/escape responses of rats submitted to aversive stimulation of the dorsolateral periaqueductal gray (dPAG) were recorded following intraperitoneal injection of three chemically unrelated but selective 5HT2C receptor agonists (Ro 60-0175, Org 12962 and Ro 60-0332) and fluoxetine. The decreased sensitivity of rats to the acute panic-like aversion elicited by stimulation of this limbic periventricular region was detected at dosages devoid of impairing effects on the latencies needed for operant brain stimulation interruption. In this paradigm which has been validated as a simulation of acute anxiety with relevance to panic disorder, the selective activation of 5HT2C receptors by Ro 60-0175, Org 12962 or Ro 60-0332 induces effects analogous to those observed following benzodiazepine receptor activation by antipanic agents such as clonazepam or alprazolam or following non-selective and indirect 5HT receptor activation by fluoxetine. Potency and efficacy of 5HT2C receptor agonists were intermediate between those of clonazepam and fluoxetine, indicating authentic antiaversive properties and suggesting antipanic potential for these 5HT2C receptor agonists. In addition, these data suggest that the 5HT2C receptor subtype may play a major role in the therapeutic properties of selective serotonin reuptake inhibitors. It is also speculated that serotonin/benzodiazepine interactions existing in the brain may functionally involve the 5HT2C receptor subtypes and that the anxiogenic action reported under certain circumstances for 5HT mimetics are not mediated by 5HT2C receptor subtypes.

Animals↗
PubMed1998

5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential.

In vitro, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 exhibited high-affinity binding to the serotonin2C (5HT2C) receptors and stimulated turnover of inositol 1,4,5-triphosphate. Affinity to several of the other 5-HT receptor subtypes and to numerous nonserotonergic receptors was much lower. In rats, both compounds elicited behavioral signs of 5-HT2C receptor agonism but not 5-HT2A receptor agonism. Hypomotility induced in rats by high doses of these compounds was reversed by the 5-HT2C receptor antagonist N-(2-naphthyl)-N'-(3-pyridyl)-urea 1:1 HCI. In addition, these compounds were active in tests used to demonstrate anticompulsive effects: reducing schedule-induced polydipsia in rats (prevented by the 5-HT2C/2B receptor antagonist N-(1-methyl-5'-indolyl)-(3-pyridyl)urea 1:1 HCl, reversing increased scratching induced with 8-hydroxy-dipropylaminotetralin 1:1 HCl in squirrel monkeys (no tolerance developed), decreasing responding in the marble-burying task in mice, and decreasing excessive eating of palatable food in rats. In contrast to these compounds, fluoxetine was much less potent, and in some tasks less efficacious, in reducing excessive behavior in these models. These two 5-HT2C receptor agonists do not show anxiogenic effects in the plus-maze in rats. (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 reduced the olfactory bulbectomy-induced passive avoidance impairment in rats, a result that indicates antidepressant potential. Similarly, in the differential-reinforcement-of-low rate 72-s operant schedule task in rats, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 increased (and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 showed a tendency to increase) total reinforcements received, which is suggestive of antidepressant activity. The electroencephalography defined sleep-waking pattern in rats produced by these two 5-HT2C agonists, as well as fluoxetine, included increased quiet-waking and decreased rapid-eye-movement sleep, which is characteristic of antidepressant drugs. These results suggest that 5-HT2C receptor agonism is associated with therapeutic potential in obsessive compulsive disorder and depression.

Animals↗
PubMed1997

Indirect in vivo 5-HT1A-agonistic effects of the new antidepressant mirtazapine.

The new antidepressant mirtazapine was tested in two experimental procedures which can reveal direct or indirect 5-HT1A receptor agonistic effects. These procedures were observation for induction of lower lip retraction in rats and comparison of stimulus properties in cross-familiarization experiments with conditioned taste aversion in mice. Mirtazapine induced lower lip retraction in rats, as did the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). However, the response to mirtazapine at doses up to 22 mg/kg remained below the maximum score obtained with 8-OH-DPAT (0.46 mg/kg). Blockade of the 5-HT1A receptors with pindolol (10 mg/kg) caused a strong reduction of the lower lip retraction induced both with mirtazapine and 8-OH-DPAT. In the cross-familiarization conditioned taste aversion experiments it was found that the conditioned taste aversion induced by mirtazapine (0.32 mg/kg) could be prevented if the mice were pre-exposed to injections with mirtazapine (0.22 and 0.46 mg/kg), 8-OH-DPAT (0.22 and 0.46 mg/kg) and after pre-exposure to the 5-HT reuptake inhibitor fluoxetine (22 mg/kg). No familiarization for the mirtazapine stimulus was obtained by pre-exposure to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) (0.46-4.6 mg/kg) and MK212 (2.2-22 mg/kg), being agonists for the 5-HT2A and 5-HT2C receptors, respectively. With the reversed sequence, the conditioned taste aversion induced by 8-OH-DPAT (0.22 mg/kg), DOI (1.0 mg/kg) and fluoxetine could be prevented only partially by pre-exposure to mirtazapine in a dose of 1 mg/kg. The conditioned taste aversion induced by MK 212 (4.6 mg/kg) was not affected by pre-exposure to mirtazapine (0.1-1.0 mg/kg). On the basis of these results, it can be concluded that mirtazapine has indirect 5-HT1A receptor agonistic properties which may play an important role in the therapeutic effect of this compound.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Modulation of 5-HT receptor subtype-mediated behaviours by corticosterone.

Malfunction of the serotonergic system and dysregulation of the hypothalamo-pituitary-adrenocortical axis have been implicated in the pathophysiology of depression. Several studies provide evidence for reciprocal influences between glucocorticoids and 5-HT receptors. The effect of repeated treatment with a high dose of corticosterone (50 mg/kg s.c. twice daily for 4 days) on 5-HT receptor subtype-mediated behaviours was studied. It was found that in rats that were repeatedly treated with corticosterone the number of 2-chloro-6-(1-piperazinyl)pyrazine HCl (MK 212)-induced, 5-HT2C receptor-mediated penile erections were reduced, whereas both MK 212 and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced 5-HT2A receptor-mediated head shakes were increased. The (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced lower lip retraction mediated by presynaptic 5-HT1A receptors was unchanged, whereas the open field activity induced by 8-OH-DPAT was enhanced in corticosterone pretreated rats. These changes in 5-HT receptor subtype-mediated behaviours were not seen after a single injection with corticosterone given 24 h or 5 days before. The results suggest that 5-HT2A, 5-HT2C and postsynaptic 5-HT1A receptor-mediated behaviour can be modulated by repeated treatment with a high dose of corticosterone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory.

The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain-dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Role of dorsal and median raphe nuclei in lower lip retraction in rats.

Induction of lower lip retraction after local infusion of the selective 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the dorsal and median raphe nuclei was measured. Infusion of 8-OH-DPAT (2.5, 5 and 10 micrograms/rat) into the median raphe nucleus caused an immediate and dose-dependent lower lip retraction. After infusion into the dorsal raphe nucleus a higher dose was needed. The lowest dose of 8-OH-DPAT that induced lower lip retraction was 10 micrograms/rat. Infusion of 8-OH-DPAT (10 micrograms/rat) into the pontine reticular nucleus induced the same degree of lower lip retraction as seen after infusion of the compound into the dorsal raphe nucleus. 8-OH-DPAT-induced lower lip retraction was attenuated by s.c. injection of the preferential 5-HT2C receptor agonist m-chlorophenyl-piperazine. The results suggest that lower lip retraction is mediated by 5-HT1A receptors in the median rather than in the dorsal raphe nucleus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Comparison of stimulus properties of fluoxetine and 5-HT receptor agonists in a conditioned taste aversion procedure.

Pre-exposure to 5-hydroxytryptamine (5-HT) receptor agonists in conditioned taste aversion experiments was used to characterize the stimulus properties of fluoxetine. The taste aversion induced by fluoxetine (10 mg/kg) was completely prevented when mice were pre-exposed to fluoxetine or when they were pre-exposed to the preferential 5-HT1C receptor agonist MK 212. Pre-exposure to MK 212 also prevented the conditioned taste aversion induced by another serotonin uptake inhibitor, paroxetine. A partial attenuation of fluoxetine-induced conditioned taste aversion was seen after pre-exposure to a high dose of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 1 mg/kg), but not to lower doses. No familiarization for the fluoxetine stimulus was obtained by pre-exposure to treatments with the mixed 5-HT1C/2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). With the reversed sequence, pre-exposure to fluoxetine prevented the conditioned taste aversion induced by MK 212 or 8-OH-DPAT and reduced that induced by DOI. It is concluded that the acute stimulus properties of fluoxetine mostly resemble those of a 5-HT1C receptor agonist. This supports the suggestion that the 5-HT1C receptor can play an important role in the therapeutic effect of 5-HT reuptake inhibitors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Involvement of corticosteroids in the processing of stressful life-events. A possible implication for the development of depression.

In a sub-population of endogenously depressed patients, disturbances of the hypothalamic-pituitary-adrenal axis can be observed. Increased cortisol and CRH levels combined with normal ACTH concentrations have often been reported. Corticosteroids appear to play a role in the mood changes, in depressed subjects. However, their mechanism of action is unknown. In animal experiments, the involvement of corticosteroids in stressor-induced learning was investigated. Three paradigms were used. In the Porsolt swimtest an animal had to learn to adapt to an inescapable situation. In the lithium chloride conditioned taste aversion an animal learned to avoid sugar water. In the amphetamine sensitization a second injection of amphetamine caused a potentiated response, because of conditioning. All three conditions appeared to be stressful because they induced a corticosterone release. When adrenalectomized (ADX) mice were compared to control animals it appeared that, in all three paradigms, their memory function was disturbed. The data indicated that this was a specific glucocorticoid-mediated effect since corticosterone and dexamethasone injections were able to reverse the ADX-induced deficit. The ADX-induced disturbances were only observable at moderate stress levels. More severe stressors (lower water temperature in the Porsolt swimtest, higher lithium chloride and amphetamine doses) also made ADX mice remember their previous experiences. The results suggest that corticosteroids are involved in the consolidation of stressful events and the corresponding coping responses. They play, however, only a role in the case of moderate stressors. In ADX animals no stressor-induced corticosterone increase can occur and therefore these animals only remember severe stressors. In a depressed patient basal steroid levels are increased and consequently very mild stressors, which induce only a small extra steroid release, will be remembered. The remembering of all these negative experiences might be of importance for the development and maintenance of the depression.

Adrenal Cortex Hormones↗
PubMed1993

Electromyographical differentiation of the components of perioral movements induced by SKF 38393 and physostigmine in the rat.

Facial electromyography (EMG) coupled with visual observation was used to investigate spontaneous and drug induced perioral movements in freely moving rats. Four separate perioral behaviours were identified; facial tremor, purposeless chewing, gaping and yawning. Facial tremor, yawning and gaping but not purposeless chewing produced characteristic EMG signals. Normal rats displayed a low level of purposeless chewing, occasional bursts of facial tremor but not gaping or yawning. Each burst of facial tremor was accompanied by a transient increase in purposeless chewing. Administration of the D1 agonist SKF 38393 induced a dose related increase in bursts of facial tremors and consequently an increase in the total number of purposeless chews. Gaping and yawning were not induced by SKF 38393 administration. Administration of the cholinesterase inhibitor physostigmine (0.1-0.4 mg/kg) induced a dose related increase in the total number of purposeless chews, but primarily these were not associated with facial tremor. Administration of physostigmine also increased gaping and yawning. Administration of the D1 antagonist SCH 23390 almost abolished facial tremor in normal treated rats but only partially reduced that induced by SKF 38393 and physostigmine. SCH 23390 reduced purposeless chewing in SKF 38393 treated rats but not in normal or physostigmine treated animals. Administration of the cholinergic antagonist atropine almost abolished facial tremor in normal and physostigmine treated rats, but only reduced by 46% that induced by SKF 38393. Atropine reduced purposeless chewing in normal, physostigmine and SKF 38393 treated animals. Physostigmine induced gaping and yawning were abolished by atropine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Effect of chronic trifluoperazine administration and subsequent withdrawal on the production and persistence of perioral behaviours in two rat strains.

The effect of chronic administration of trifluoperazine on the perioral movement profile of Wistar and Sprague-Dawley rats was examined. Perioral movements were characterised by visual observations, coupled with electromyographic recording from the masseter muscle. In drug-naive animals from both strains the spectrum of perioral behaviours was essentially identical, primarily consisting of purposeless chewing, accompanied by occasional bursts of facial tremor and teeth chattering, with occasional yawning. Each burst of facial tremor was accompanied by a transient increase in the rate of purposeless chewing. Wistar rats exhibited a higher level of spontaneous purposeless chewing compared to Sprague-Dawley rats. In both strains, chronic administration of trifluoperazine (5 mg/kg per day, PO) for 5 months induced an increase in perioral behaviour, which primarily consisted of enhanced purposeless chewing. In Wistar rats the drug-induced increase in purposeless chewing was accompanied by an increase in the incidence of yawning, with no change in the incidence of either facial tremor or teeth chattering. In contrast, Sprague-Dawley rats displayed a drug-induced increase in purposeless chewing, accompanied by an increase in the incidence of facial tremor and teeth chattering, but not yawning. In Wistar rats withdrawal of trifluoperazine diminished but did not reverse the drug-induced increase in purposeless chewing. Drug withdrawal also precipitated a transient increase in the incidence of facial tremor and teeth chattering, but had no effect on yawning. In Wistar rats, the level of purposeless chewing and the incidence of yawning remained elevated above control levels for at least 13 weeks after drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cross-familiarisation conditioned taste aversion procedure as a method to reveal stimulus resemblance between drugs: studies on the 5-HT1A agonist 8-OHDPAT.

In the present study a cross-familiarisation conditioned taste aversion (CTA) paradigm was utilized to reveal stimulus resemblance between the selective 5-HT1A agonist 8-OHDPAT and a variety of serotonergic and non-serotonergic drugs. In male mice, a 0.22 mg/kg dose of 8-OHDPAT was used as the reference compound inducing CTA. Dose-dependent effects of pre-exposure to 24 different test drugs on the magnitude of the 8-OHDPAT-induced CTA were tested as a measure for stimulus similarity between these test drugs and 8-OH-DPAT (the reference compound). Pre-exposure to 8-OH-DPAT itself, ipsapirone, buspirone, RU 24969, sertraline, d-amphetamine, LSD, metergoline and idazoxan effectively prevented the development of CTA induced by 8-OHDPAT. Pre-exposure to apomorphine, diazepam, SCH 23390, LiCl, spiperone, DOI, spiroxatrine, umespirone, pindolol, mCPP, haloperidol, MK 212, clonidine, quipazine and also 5-MeODMT was not effective in completely abolishing the CTA produced by 8-OHDPAT. It is concluded from these results that the relatively simple and fast cross-familiarisation taste aversion method is a suitable paradigm to study similarities in stimulus properties of different drugs.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Stimulus characterization of estradiol applying a crossfamiliarization taste aversion procedure in female mice.

In female mice (n = 240), the estradiol stimulus was characterized by studying preexposure effects of sex steroids and sickness-inducing drugs on estradiol-induced (50 micrograms/kg SC) conditioned taste aversion (CTA). It was established that preexposure to estradiol itself (2-50 micrograms/kg SC) attenuates the development of CTA produced by the hormone. Only partial crossfamiliarization effects were found with progesterone (50-200 micrograms/kg SC) and testosterone (250-1000 micrograms/kg SC), steroids that induce CTA themselves. Preexposure to the sickness-inducing drugs lithium chloride (22 mg/kg SC) and apomorphine (0.1-0.2 mg/kg SC) prevented or substantially reduced the development of estradiol-induced CTA, respectively. It was concluded that only a low degree of stimulus resemblance exists between estradiol and the other principal sex steroids, progesterone and testosterone. In addition, it was concluded that the estradiol stimulus resembles the stimuli produced by sickness-inducing drugs.

Animals↗
PubMed1992

The involvement of glucocorticoids in the acquired immobility response is dependent on the water temperature.

The Porsolt swim test was used to study the role of glucocorticoids in a simple learning paradigm. Two experiments were performed. In the first experiment, the stressfulness of the situation was manipulated by testing control, sham-operated and adrenalectomized mice at different water temperatures (20 degrees C, 25 degrees C, 30 degrees C and 35 degrees C). In the second experiment, control mice were injected with the glucocorticoid antagonist RU38486 (3.2 mg/kg, 10 mg/kg, 32 mg/kg); adrenalectomized mice were injected with the glucocorticoid agonists corticosterone (0.46 mg/kg, 1.0 mg/kg, 2.2 mg/kg) and dexamethasone (0.005 mg/kg, 0.05 mg/kg, 0.1 mg/kg). The results show that water temperature is a very important factor in the Porsolt swim test. It influences the overall behaviour of the animals and changes the involvement of glucocorticoids. At a water temperature of 25 degrees C, glucocorticoids play an important role in the retention of the immobility response; ADX mice are impaired, and this impairment can be ameliorated by corticosterone and dexamethasone injection. Furthermore, the impairment can be induced in control mice by RU38486. The effects observed at 25 degrees C were, however, not observable at 20 degrees C, 30 degrees C and 35 degrees C, which suggests, contrary to previous reports, that glucocorticoids do not play a universal role in retention processes.

Adrenal Glands↗
PubMed1992

Sex steroids possess distinct stimulus properties in female and male mice.

Very few studies have investigated the aversive properties of sex steroids in animals. We studied these properties by testing oestradiol-3-benzoate, testosterone-propionate and progesterone in a conditioned taste aversion set-up, in intact female and male mice. Oestradiol-3-benzoate induced a taste aversion in both female and male mice; however, testosterone-propionate and progesterone had an effect only in females. These results show that sex steroids have intrinsic aversive properties. The different effects of the steroids in males and females cannot simply be explained by nausea induction or novelty.

Analysis of Variance↗