Biomedical subjects
Publications and source records attributed to K Larsson.
The GABA antagonist (+) bicuculline methiodide (30 ng/cannula) was injected in the medial preoptic-anterior hypothalamic area of castrated rats treated with subthreshold dosages of testosterone propionate (150 micrograms/kg/day). The treatment resulted in a facilitation of sexual activity suggesting a role of GABA as a neurotransmitter in neural processes determining sexual arousal.
Drugs affecting the GABAergic transmission were injected into the medial preoptic anterior hypothalamic area (MPOA) and the masculine sexual behavior analyzed. Antagonizing GABAergic neurotransmission by (+) bicuculline methiodide (30 ng/cannula), or 3-mercaptopropionic acid (10 or 20 micrograms/cannula) resulted in a drastic shortening of the postejaculatory intervals and a shortening of the ejaculation latency. Injection of compounds causing an increase in GABAergic activity, muscimol (25 ng/cannula) or ethanolamine-O-sulphate (80 micrograms/cannula) depressed masculine sexual behavior. Systemic treatment or injection into the nucleus caudatus putamen of compounds affecting the GABAergic transmission did not cause any alteration in the mating pattern. It is suggested that the GABAergic neurotransmission is involved in inhibitory processes underlying the masculine sexual behavior.
gamma-Aminobutyric acid (GABA) (1.0 microgram/cannula) or muscimol (50 ng/cannula) was injected into the ventromedial hypothalamus or the lateral septi nuclei of ovariectomized rats brought to sexual receptivity by combined treatment of estrogen and progesterone. No inhibitory effects of GABA or muscimol were observed on the lordosis behavior. Furthermore, systemic (1.0 mg/kg) or intrahypothalamic (50 ng/cannula) picrotoxin administration was followed by a statistically significant increase in lordosis behavior in ovariectomized, estrogen-primed rats. No such effect was observed in ovariectomized-adrenalectomized animals, indicating its dependence on adrenal secretions. Present results do not support the hypothesis of a GABAergic mechanism in the hormonal control of lordosis behavior.
The male rat emits ultrasonic (22 kHz) vocalizations after ejaculation and behavioural and electrophysiological evidence suggests that this vocalization reflects an inhibitory state underlying and determining the postejaculatory refractory period (PEI). Present results show that injection into the preoptic-anterior hypothalamic area of (+)-bicuculline methiodide, a GABA antagonist, shortens the PEI and reduces ultrasonic vocalization. It is suggested that the suppression of ultrasonic vocalization following bicuculline treatment reflects a depression of an inhibitory state normally produced by ejaculation.
Bronchoalveolar lavage (BAL) was performed on nine healthy nonsmoking subjects and on 11 healthy smokers; in the last mentioned group lavage was performed before and after eight weeks treatment with N-acetylcysteine (NAC; 200 mg t.i.d.). The BAL cells were cultured for 2 h or overnight. Adherent cells were examined for their capacity to generate superoxide radicals (determined by superoxide dismutase (SOD)-inhibitable cytochrome C-reduction) at stimulation with phorbol 12-myristate 13-acetate (PMA), serum-treated zymosan (STZ), the calcium ionophore A23187, or the chemotactic tripeptide formyl-methionylleucylphenylalanine (FMLP). Cells from nonsmokers responded with a very low degree of O(2)-generation to any of the stimuli employed whether cultured for 2 h or overnight. Cells from smokers also responded with low O(2)-generation after 2 h of culture. However, cells from smokers cultured overnight responded with marked O(2)-generation to PMA and STZ but the responses to FMLP and A23187 were low. NAC-treatment of the smokers resulted in a reduced degree of both PMA- and STZ-induced O(2)-generation in five individuals. In two other subjects, PMA-induced (but not STZ-induced) O(2)-generation was reduced. Two individuals showed increased O(2)-generation to PMA- and to STZ-stimulation after NAC-treatment. Mean values of O(2)-generation induced by A23187 or by FMLP were significantly reduced for cells harvested after NAC-treatment. Mean values for PMA-induced O(2)-generation also tended to be reduced by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of circulating noradrenaline (in this context primarily a non-selective alpha agonist) and the alpha 1 selective agonist phenylephrine on bronchial tone, blood pressure, and heart rate was studied in eight patients with exercise induced asthma and eight age and sex matched controls. All subjects refrained from taking treatment for at least one week before the trial. The agonists were infused intravenously in stepwise increasing doses of 0.04, 0.085, 0.17, and 0.34 micrograms/kg a minute for noradrenaline and 0.5, 1.0, 2.0, and 4.0 micrograms/kg a minute for phenylephrine. At the highest dose the plasma concentration of noradrenaline was about 30 nmol/l, resembling the concentrations found during intense exercise, and that of phenylephrine was about 400 nmol/l. Both agonists caused dose dependent and similar increases in blood pressure in the two groups. Despite clearcut cardiovascular effects (systolic and diastolic blood pressure increased by about 40-50/25-30 mm Hg), neither agonist altered lung function, as assessed by measurements of specific airway compliance (sGaw), peak expiratory flow (PEF), or end expiratory flow rate, in either group. It is concluded that circulating alpha agonists, whether alpha 1 selective (phenylephrine) or non-selective (noradrenaline), fail to alter basal bronchial tone in patients with exercise induced asthma or in healthy subjects.
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The influence of circulating noradrenaline on bronchial reactivity to histamine was investigated in eight asthmatic patients. Bronchial hyperreactivity was confirmed by a pretrial bronchial histamine challenge which was positive at a concentration below 6 mg/ml in all patients. On two separate occasions bronchial challenge tests were performed during infusions of placebo (saline) or noradrenaline (0.25 micrograms X kg-1 X min-1). The latter infusion elevated venous plasma noradrenaline concentrations from 2.5 +/- 0.3 to 27.4 +/- 3.3 nmol/l and increased blood pressure by 30/17 mm Hg. The effects of noradrenaline and placebo did not differ with regard to any lung function parameter. Histamine inhalations induced bronchoconstriction (greater than 60% reduction of Sgaw) and elevated heart rate by 11 beats/min, but did not alter venous plasma adrenaline concentrations. The bronchial reactivity to histamine was similar during placebo and noradrenaline infusions. High levels of circulating noradrenaline do not alter basal airway calibre or the bronchial reactivity to histamine in asthmatic patients.
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Intracerebral infusion of (+) bicuculline methiodide, but not of its (-) isomer, in the preoptic area, stimulated masculine sexual behavior in rat as evidenced by a decrease in the number of intromissions preceding ejaculation and a shortening of the ejaculation latency and postejaculatory interval. Data suggest a role of the GABAergic system in mediating masculine sexual behavior.
Both lisuride and 8-OH-DPAT dose dependently antagonized the 5-HTP-induced inhibition of male rat sexual behavior. The increase in the number of intromissions and/or the ejaculation latency produced by 5-HTP, 25 mg/kg i.p. (-60 min) in combination with the peripheral 5-HTP decarboxylase inhibitor benserazide, 25 mg/kg i.p. (-90 min), were antagonized by lisuride, 0.05-0.1 mg/kg i.p. (-15 min) and by 8-OH-DPAT, 0.025-0.05 mg/kg i.p. (-15 min). Thus, in this model lisuride and 8-OH-DPAT behave as 5-HT antagonists.
Weanling rats were treated with diazepam, apomorphine, and haloperidol to study the influence of the dopamine (DA) system on the audiogenic immobility reaction and open field locomotory behavior. Treatment with diazepam (0.025, 0.05, and 0.1 mg/kg) caused a dose-dependent shortening of the duration of the immobility response. Treatment with apomorphine (0.125, 0.25, and 0.50 mg/kg) shortened both the immobility reaction and the latency to leave the spot where the animal was first placed in the open field (latency for first crossing). Locomotor activity increased in a dose-dependent fashion. Both grooming and rearing showed biphasic dose response curves, with a maximum occurring at the 0.125 mg/dose for grooming and at the 0.25 mg/dose for rearing. Haloperidol (0.06 mg/kg) exerted opposite effects to those of apomorphine, but also produced increased running during the auditory stimulation (flight distance). Using the immobility reaction as an expression of fear, we concluded that activation of the DA system decreases while inhibition of the DA system increases fear. It was hypothesized that the DA system exerts an inhibitory function in the expression of fear.
Oxotremorine (0.1-0.8 mg/kg IP), but not arecoline (12-48 mg/kg IP), or pilocarpine (5-20 mg/kg IP), reduced both the number of intromissions to ejaculation and the ejaculation latency in methscopolamine-pretreated male rats. The effects of oxotremorine, (0.4 mg/kg IP) were completely antagonized by the administration of scopolamine (0.4 mg/kg IP). Methscopolamine (3-12 mg/kg IP), or scopolamine (0.2-0.4 mg/kg IP) did not by themselves produce any statistically significant effects on male rat sexual behavior.
Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with inbred normotensive rats of the Wistar-Kyoto strain (WKY) and with normally bred Wistar rats (NT) in tests on the audiogenic immobility reaction (freezing), open-field behavior in a dark and an enlightened arena respectively, auditory startle response and male sexual behavior. Compared to the WKYs the SHRs showed increased locomotion and rearing in the open-field situations, reduced startle response and shortened immobility reaction. The SHRs differed in the same way from the NT rats with the exception for motor activity in the dark arena, where no differences were observed. The WKY rats showed less motor activity than the NT animals. Both SH and WKY rats showed shorter latency time for ejaculation than the NT rats. The characteristics of the behavior patterns displayed by the SH rats were interpreted as indicating a reduced propensity for fear reactions in this strain of rats compared to the WKY and NT strains used in the present study.
Ovariectomized (OVX) and ovariectomized-adrenalectomized (OVX-ADX) rats were injected with estradiol benzoate (EB, 4.0 micrograms/rat) and received 44 hr by infusion into the ventromedial hypothalamic area one of the following treatments: norepinephrine (NE), clonidine (an alpha-agonist), isoproterenol (a beta-agonist) or a combination of clonidine and isoproterenol. Infusion of NE (200 ng/rat) induced lordosis in both OVX and OVX-ADX rats 15 minutes after its administration. NE-induced lordosis was blocked by systemic treatment with either the alpha-antagonist, prazosin (1.0 mg/kg), or the beta-antagonist, propranolol (4.0 mg/kg). Intrahypothalamic infusion of clonidine (200 ng/rat) or isoproterenol (200 ng/rat) induced lordosis behavior in OVX, but not in OVX-ADX rats, suggesting the involvement of adrenal secretions in this response. Combined administration of clonidine (100 ng/rat) and isoproterenol (100 ng/rat) induced lordosis behavior 15 minutes after its intrahypothalamic infusion in OVX-ADX animals. Results are discussed in relation to a model proposed for the induction of lordosis behavior involving steroid-NE interactions.
The effect of systemic administration of adrenergic alpha (phenoxybenzamine and prazosin) and beta (propranolol) antagonists on the lordosis behavior induced by progesterone (2.0 mg/rat) was studied in ovariectomized estradiol benzoate (4.0 micrograms/rat) primed rats. The effect of these antagonists was also tested on the lordosis behavior induced in ovariectomized rats by estradiol benzoate alone (1.25 micrograms/rat each two days). Phenoxybenzamine (0.8, 4.0 and 20.0 mg/kg), propranolol (0.8, 4.0 and 20.0 mg/kg) and prazosin (0.2 and 1.0 mg/kg) caused a dose-dependent reduction of progesterone induced lordosis. By contrast, phenoxybenzamine (4.0 mg/kg), propranolol (4.0 mg/kg) or prazosin (1.0 mg/kg) did not affect estrogen induced lordosis behavior. Results suggest the following conclusions: (1) blockage of either alpha or beta adrenoreceptors prevents progesterone induced lordosis behavior and (2) the adrenergic neuron involved in progesterone facilitation of lordosis behavior is not a part of the reflex arc for lordosis but probably modulates the activity of this system.
The influence of circulating epinephrine on basal bronchial tone and its ability to counteract the bronchial response to specific allergen challenge was investigated in eight patients with extrinsic seasonal asthma. A pretrial bronchial allergen challenge was positive for birch or timothy pollen. The patients were free from all medication at least 1 wk before experiments. On two separate occasions placebo (saline) or epinephrine (0.25 and 0.50 nmol X kg-1 X min-1) were infused. Epinephrine caused dose-dependent increases in end expiratory flow rates but did not influence peak expiratory flow rates or specific airway conductance, indicating dilatation of predominantly smaller airways. During placebo infusions allergen provocation induced clear-cut bronchoconstriction but no increase in circulating epinephrine levels. Elevation of circulating epinephrine (to 5 to 6 nmol/L in venous plasma) counteracted the allergen-induced bronchoconstriction. During epinephrine infusions all patients tolerated higher allergen doses than during placebo infusions. When the allergen dose was increased sufficiently to cause bronchoconstriction also during epinephrine infusions, the bronchoconstriction observed was similar in terms of changes in lung function parameters but less responsive to treatment with a high dose of the beta-2-agonist, salbutamol. This may have therapeutic implications since protection offered by treatment with, e.g. beta 2-agonists, may lead to exposure to higher allergen doses and similarly aggravated asthmatic reactions when they do occur despite this treatment.
Female rats were given 16% ethanol solution as the sole liquid during the entire period of gestation. At birth the offspring was removed and reared by foster dams consuming normal tap water. At adult age the female offspring showed deficiencies in their maternal behaviour; they built nests of poor quality and they displayed prolonged times for retrieving pups placed outside the nest. In the whole brains of the prenatally ethanol-exposed females a decreased serotonin synthesis was observed. The offspring of the prenatally ethanol exposed mothers did not show any signs of disturbances in physical or behavioural development.