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S Ahlenius

Publications and source records attributed to S Ahlenius.

At least 19 recordsLinked to original sources
PubMed1998

Sexual motivation promotes oxytocin secretion in male rats.

The present study examines plasma oxytocin levels in relation to performance of copulatory behavior in male rats. The animals were divided into three groups: A) home-cage controls, B) sexually naive and C) sexually experienced. Following 15 min of sexual interactions with a sexually proceptive female, brought into estrus by sequential injections of estradiol benzoate (12.5 micrograms animal-1, -48 h) and progesterone (0.5 mg animal-1, -6 h), the male rats were decapitated. Trunk blood was collected for preparation of plasma samples, and subsequent radioimmunoassay for oxytocin. Home-cage controls, not exposed to a sexually proceptive female, were decapitated at the same time as experimental animals. It was found that plasma oxytocin levels were significantly elevated in sexually naive rats following exposure to a sexually proceptive female, and that plasma oxytocin levels were highly correlated with intensity of copulatory performance in these animals. In addition, it was also found that plasma prolactin and glucose levels were increased, regardless of sexual experience, in comparison with home-cage controls. It is concluded that the emotional challenge, and the situation-specific demands for action, created by an encounter with a sexually proceptive female, are accompanied by an increased plasma concentration of oxytocin in sexually naive, but not sexually experienced, male rats.

Animals↗
PubMed1998

Steroid dependent effects of oxytocin on spontaneous motor activity in female rats.

In the present study, dose relationships for effects of oxytocin (OXY) on spontaneous motor activity in female rats were investigated. Ovariectomized (OVX) and cycling female Sprague-Dawley rats were given OXY 10-1000 microg/kg s.c. or saline, 10 min before registration of motor activity in an open-field arena. In the OVX rats, 100 microg/kg of OXY increased the activity in the center of the arena, whereas 1000 microg/kg decreased locomotor activity (LA). In the cycling rats, OXY 100-1000 microg/kg decreased LA during diestrus, while 1000 microg/kg also decreased LA during metestrus. The latter dose also reduced the exploratory behavior during estrus. In a second experiment, OVX rats were pretreated with estradiol benzoate (EB) and progesterone (P). When P levels were predominant, OXY 10-1000 microg/kg decreased LA. Oxytocin 10-100 microg/kg given after pretreatment with EB increased the activity in the center of the arena, whereas 1000 micro/kg given in the presence of both EB and P increased peripheral activity (PA). These results show that the effects of OXY on motor activity in female rats are modified by female sex steroid hormones.

Analysis of Variance↗
PubMed1998

Evidence for functional interactions between 5-HT1A and 5-HT2A receptors in rat thermoregulatory mechanisms.

The present study was designed to examine 1) functional interactions between 5-HT1A and 5-HT2A/C receptors in thermoregulation in rats and 2) the specific involvement of 5-HT2A and 5-HT2C receptors in such interactions. The 5-HT2A/C receptor agonist DOI (0.025 1.6 mg kg-1, subcutaneously) produced a dose-dependent hyperthermia in rats, which was enhanced by addition of either of two 5-HT1A receptor antagonists, (-)-pindolol (0.5-1.0 mg kg-1, subcutaneously) or WAY-100,635 (0.1-0.4 mg kg-1, subcutaneously). Furthermore, the DOI-induced hyperthermia was counteracted by pretreatment with the 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg kg-1, subcutaneously). The hyperthermia produced by DOI, alone or in combination with WAY-100,635, was fully antagonized by pretreatment with the 5-HT2A/C receptor antagonist ritanserin (1.0 mg kg-1, subcutaneously), as well as with the selective 5-HT2A receptor antagonist amperozide (2.0 mg kg-1, subcutaneously). The present results provide evidence for functional interactions between 5-HT1A and 5-HT2A receptors in temperature regulation in rats, and also suggest an important role for postsynaptic 5-HT2A receptors in the mediation of DOI-induced hyperthermia.

Amphetamines↗
PubMed1997

Dihydrexidine produces hypothermia in rats via activation of dopamine D1 receptors.

The selective dopamine D1 receptor agonist dihydrexidine (2.0-8.0 mg/kg, s.c.) caused a dose-dependent decrease in core temperature in rats. The hypothermia produced by dihydrexidine (4.0 mg/kg), was completely blocked by the dopamine D1 receptor antagonists SCH 23390 (0.1 mg/kg, s.c.) or NNC 687 (4.0 mg/kg, s.c.), but not by the dopamine D2/3 receptor antagonist raclopride (0.2 mg/kg, s.c.). Neither of the dopamine antagonists by themselves produced any effects on core temperature. The present results provide important evidence for the notion that activation of dopamine D1 receptors induces hypothermia in rats.

Animals↗
PubMed1997

Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin.

Intracerebroventricular (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D2 receptors measured with [3H]raclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopride-mediated suppression of spontaneous locomotor activity was attenuated, and (+/-)-7-hydroxy-dipropyl-aminotetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D2 receptor increase comprises receptors localized both post- and presynaptically. The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.

Animals↗
PubMed1997

Potentiation of DOI-induced forward locomotion in rats by (-)-pindolol pretreatment.

The present experiments were undertaken in order to examine mechanisms of action for reported interactions between the beta-blocker (-)-pindolol and serotonergic agents. It was found that pretreatment with (-)-pindolol (2 mg kg-1 s.c.) potentiated the stereotyped forward locomotion induced by the 5-HT2A/C receptor agonist DOI (0.125-1.0 mg kg-1 s.c.) in rats observed in an open-field arena. This (-)-pindolol/DOI-induced stereotyped forward locomotion was fully antagonized by the 5-HT2A/C receptor antagonist ritanserin (2 mg kg-1 s.c.), suggesting that (-)-pindolol enhances serotonin release, resulting i.a. in postsynaptic 5-HT2A/C receptor activation. This effect by (-)-pindolol is in all probability indirect since this compound lacks affinity for 5-HT2A/C receptors, and could be explained by reported antagonism of inhibitory serotonergic somato-dendritic 5-HT1A autoreceptors, although other possibilities related to 5-HT1B receptors or beta-adrenoceptors can not be excluded at this time. Furthermore, (-)-pindolol treatment also enhanced 5-HTP-induced (12.5-100 mg kg-1 i.p.) effects on spontaneous motor activity. These effects, however, were of smaller magnitude, and less consistent than those seen in combination with DOI.

Adrenergic beta-Antagonists↗
PubMed1997

Biphasic effects of 8-OH-DPAT on endurance of treadmill performance in the male rat.

Administration of the 5-HT1A receptor agonist 8-OH-DPAT produced a biphasic pattern of effects on endurance performance of rats walking on top of a treadmill drum ([symbol: see text] = 166 mm, 16 rpm; approximately 8 m min-1), with enhanced performance at a low dose (0.1 mg kg-1 s.c.) followed by impairment (0.2-0.8 mg kg-1). The partial 5-HT1A receptor agonist (-)-pindolol improved the performance in the low dose range (0.5-2.0 mg kg-1 s.c.), whereas a higher dose (8 mg kg-1) was ineffective. The 5-HT1A receptor antagonist WAY-100,635 produced an impaired performance at a low dose (12.5 micrograms kg-1 s.c.), with a recovery of performance at higher doses (50-200 micrograms kg-1). It is suggested that the inhibition of central serotonergic neurotransmission produced by stimulation or blockade of 5-HT1A auto- and post-synaptic receptors, respectively, results in an improved endurance performance on the treadmill, whereas stimulation of postsynaptic 5-HT1A receptors has the opposite action. In support of this contention, the impaired performance produced by a high dose of 8-OH-DPAT (0.8 mg kg-1) was antagonized by pretreatment with (-)-pindolol (2 mg kg-1 s.c.).

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Specific involvement of central 5-HT1A receptors in the mediation of male rat ejaculatory behavior.

The aminotetralin 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), pharmacologically characterized as a 5-HT1A receptor agonist, produces a pronounced decrease in ejaculation latency in the male rat. Stimulation of 5-HT receptors by a pharmacologically induced increase in the synaptic availability of 5-HT has been shown to produce the opposite effect. The 8-OH-DPAT-induced decrease in ejaculation latency is specific for this compound, and some chemically related ergot derivatives. In this paper we review the evidence in support for stimulation of serotonergic autoreceptors of the 5-HT1A receptor subtype as a mechanism of action for effects by 8-OH-DPAT on male rat ejaculatory behavior. We also present the questions posed by the fact that quinpirole and lisuride both produce 8-OH-DPAT-like effects on male rat ejaculatory behavior. The effects by quinpirole, lisuride of 8-OH-DPAT are not sensitive to pretreatment with the DA D2/3 receptor antagonist raeclopride. Continued studies will show whether the effects of quinpirole and lisuride can be related to stimulation of 5-HT1A receptors, of all these compounds have as yet undefined common properties.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

In vivo effects of remoxipride and aromatic ring metabolites in the rat.

The in vivo effects of remoxipride, in relation to some of its identified metabolites, were investigated in adult male Sprague-Dawley rats. The methods used included: (1) estimation of the in vivo rate of brain monoamine synthesis by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan after decarboxylase inhibition; (2) observations of spontaneous locomotor activity in a photocell-equipped open-field arena ( approximately 0. 5 m2); (3) treadmill locomotion ( approximately 4 m min-1); (4) inclined grid (60 degrees ) catalepsy test; (5) d-amphetamine-induced (1.0 mg kg-1) hyperlocomotion;(6) quinpirole-induced (0.4 mg kg-1) hypothermia. By use of one or more of these tests, the findings with remoxipride were as follows: First, remoxipride had a late onset of action (up to 3 h). Second, potency and efficacy depended on exposure to hepatic metabolism. Thus, intraperitoneal administration was more effective than the subcutaneous route, whereas virtually all biological effects were lost on intracerebroventricular administration. The ED50 values (micromol kg-1, neostriatal dihydroxyphenylalanine accumulation) for remoxipride and a range of its phenolic aromatic ring metabolites were: remoxipride (approximately 20), NCQ-344 (approximately 0.01), FLA-797 (approximately 0.1), FLA-908 (approximately 2.2), NCQ-436 (approximately 25) and NCQ-469 (approximately 30). Considering remoxipride as a nonclozapine atypical antipsychotic drug, together with the fact that remoxipride behaves as a prodrug in the laboratory studies above, further characterization of the pharmacodynamic profile of its metabolites remains a challenge.

Animals↗
PubMed1996

Further evidence for clozapine as a dopamine D1 receptor agonist.

Clozapine (0.625-10.0 mg kg-1 s.c.), but not the two major clozapine metabolites, N-desmethylclozapine (0.625-10.0 mg kg-1 s.c.) or clozapine-N-oxide (0.625-10.0 mg kg-1 s.c.), caused a dose-dependent decrease in core temperature in the rat. Furthermore, the clozapine-induced hypothermia (2.5 mg kg-1 s.c.) was fully antagonised by pretreatment with the selective dopamine D1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4, 5-tetrahydro-1 H-3-benzazepine-7-ol, maleate (NNC 687) (4.0 mg kg-1 s.c.). NNC 687 by itself (2.0-8.0 mg kg-1 s.c.) did not affect core temperature. The present results provide further evidence for the dopamine D1 receptor agonist properties of clozapine.

Animals↗
PubMed1996

Evidence for specific involvement of 5-HT1A and 5-HT2A/C receptors in the expression of patterns of spontaneous motor activity of the rat.

The 5-HT1A and the 5-HT2A/C receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.006-0.4 mg kg-1 s.c.) and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.05-4.0 mg kg-1 s.c.), respectively, produced a similar stereotyped forward locomotion in rats, although the intensity of the behavioral change was considerably less with DOI. The stereotyped forward locomotion was accompanied by a slight decrease in total activity, suppression of rearing behavior and an increased activity in the periphery of the open-field arena. In support of receptor specificity, the effects of 8-OH-DPAT and DOI could be antagonised by pretreatment with the 5-HT1A/B and the 5-HT2A/C receptor antagonists (-)-pindolol (2 mg kg-1 s.c.) and ritanserin (2 mg kg-1 s.c.), respectively. In addition, (-)-pindolol, but not the selective beta-adrenoceptor antagonist betaxolol, markedly enhanced the behavioral effects produced by DOI. The nature of these specific actions and interactions in terms of pre- and post-synaptic serotonergic mechanisms remains an important question.

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

Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat.

Adult male Sprague-Dawley rats were administered the 5-HT subtype selective receptor agonists 8-OH-DPAT (0.5-2.0 mg/kg), buspirone (2-8 mg/kg) (5-HT1A), TFMPP (0.125-2.0 mg/kg) (5-HT1B), DOI (0.125-2.0 mg/kg) (5-HT2A) and m-CPBG (1.25-20.0 mg/kg) (5-HT3), subcutaneously. Oxytocin, cholecystokinin (CCK), somatostatin and gastrin plasma levels were determined by standard RIA techniques 30 and 120 min after injection of the respective 5-HT receptor agonist. It was found that the 5-HT1A and the 5-HT2A/C, but not the 5-HT2B or the 5-HT3 receptor agonists produced an increase in plasma oxytocin levels and these effects were, at least partially, antagonized by the corresponding subtype selective antagonists (-)pindolol (2 mg/kg) and ritanserin (2 mg/kg), respectively, administered 10 min before 8-OH-DPAT (0.5 mg/kg) or DOI (0.5 mg/kg). The maximal response to the 5-HT1A receptor agonists (approx. 120 nmol/l) was from 8 to 5 times the maximal response to the 5-HT2A C receptor agonist. In addition, 8-OH-DPAT and DOI caused a decrease in plasma CCK levels, whereas the 5-HT1B receptor agonist TFMPP gave rise to an increase in plasma CCK levels. There were no statistically significant effects by any of the 5-HT receptor agonists on plasma somatostatin or gastrin levels under the present conditions. It is suggested that the clinical effects of new anxiolytic 5-HT1A receptor agonists, such as buspirone, to an extent may be mediated via an increased release of oxytocin.

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

Stroking of the abdomen causes decreased locomotor activity in conscious male rats.

The specific aim of the present study was to determine if stroking in conscious rats can influence spontaneous locomotor behavior in an open-field arena. For this purpose, conscious rats were held across the scapula and the ventral side of the abdomen was stroked at a pressure of 100-150 mm H2O and at a speed of approximately 20 cm/s. The stimulation frequency was approximately 40 strokes/min and the duration 2, 5, and 10 min. Animals held for 10 min served as controls. There was a significant decrease in rearing and locomotion and a significant increase in peripheral activity in the open-field arena after the treatment. Maximal effects were obtained after 5 min of stroking. These effects were consistent with a stroking-induced sedative effect similar to that seen in this open-field arena model following neuroleptics or large doses of oxytocin.

Animals↗
PubMed1996

Enhancement of antipsychotic-like properties of the dopamine D2 receptor antagonist, raclopride, by the additional treatment with the 5-HT2 receptor blocking agent, ritanserin, in the rat.

The effects of 5-HT2 receptor blockade on the ability of a dopamine (DA) D2 receptor antagonist to produce suppression of conditioned avoidance response (CAR) and to produce catalepsy in rats were examined. It was found that ritanserin (2 mg kg-1 s.c.) enhanced the raclopride (0.1 mg kg-1 s.c.)-induced suppression of CAR without affecting raclopride-induced catalepsy at either maximal (4 mg kg-1 s.c.) or submaximal (0.2 mg kg-1 s.c.) doses. Considering the CAR performance as an index of mesocorticolimbic dopaminergic functions, it is concluded that 5-HT2 receptor blockade confers a limbic profile on the DA D2 receptor antagonist.

Animals↗
PubMed1996

Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat.

Male Sprague-Dawley rats were given one of the 5-HT receptor agonists 8-OH-DPAT (0.5-2.0 mg kg-1), TFMPP (0.125-2.0 mg kg-1), DOI (0.125-2.0 mg kg-1), and m-CPBG (1.25-20.0 mg kg-1), selective for 5-HT1A, 5-HT1B, 5-HT2 and the 5-HT3 receptors, respectively, or one of the DA receptor agonists bromocriptine (2.0-32.0 mg kg-1), quinpirole (0.5-8.0 mg kg-1) and 7-OH-DPAT (0.2-3.2 mg kg-1), selective for DA D2, DA D2/D3 and DA D3 receptors, respectively. An additional group of animals was given buspirone (2.0-8.0 mg kg-1) a 5-HT1A receptor agonist and DA D2 receptor antagonist. Separate groups of rats were given both the 5-HT1A receptor antagonist pindolol and 8-OH-DPAT or both the DA D2/D3 receptor antagonist raclopride and 7-OH-DPAT. Blood samples were collected 30 min (in some cases 120 min) after drug administration and assayed for insulin, glucagon and glucose levels. The 5-HT1A receptor agonist 8-OH-DPAT produced a statistically significant decrease in plasma insulin levels and an increase in glucose, whereas glucagon levels were unaffected. The only effect observed after buspirone treatment was a small increase in plasma glucose levels. No significant effects on plasma insulin, glucagon or glucose were seen after treatment with the 5-HT1B, 5-HT2 or 5-HT3 agonists. The DA D3 receptor agonist 7-OH-DPAT produced a decrease in plasma insulin (3.2 mg kg-1, 120 min) and an increase in glucose levels. Administration of the DA D2/D3 receptor agonist quinpirole resulted only in increased plasma glucose, whereas the DA D2 receptor agonist bromocriptine had no effect. In support of a separate mediation of glucose secretion by 5-HT1A and DA D3 receptors, the effects of 8-OH-DPAT on glucose levels were antagonized by (-)pindolol pretreatment, and the 7-OH-DPAT-induced effects on glucose levels were antagonized by raclopride pretreatment. It is concluded that plasma glucose levels are under separate serotonergic and dopaminergic control, exerted via 5-HT1A and DA D3 receptors, respectively.

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

Antagonism by the 5-HT2A/C receptor agonist DOI of raclopride-induced catalepsy in the rat.

It has been shown that the administration of 5-hydroxytryptamine (5-HT)1A receptor agonists will antagonize the catalepsy induced by dopamine D1 or D2 receptor blocking agents. In the present study, administration of the 5-HT2A/C receptor agonist, 1-(2,5-dimethoxy-4-iodo)-2-aminopropane (DOI) (1 mg kg-1 s.c.), counteracted the catalepsy produced by the dopamine D2 receptor antagonist, raclopride (16 mg kg-1 s.c.), but not by the dopamine D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepine (SCH 23390) (0.2 mg kg-1 s.c.). The effects of DOI on raclopride-induced catalepsy were fully antagonized by pretreatment with the 5-HT2A/C receptor antagonist, ritanserin (2 mg kg-1 s.c.). The 5-HT precursor, 5-hydroxytryptophan (5-HTP) (6.25-25.0 mg kg-1 i.p.), in combination with the peripheral 5-HTP decarboxylase inhibitor, benserazide (25 mg kg-1 i.p.), and the selective serotonin reuptake inhibitor, zimeldine (10 mg kg-1 s.c.), enhanced the catalepsy produced by a low dose of raclopride (4 mg kg-1 s.c.). It is concluded that stimulation of (postsynaptic) 5-HT2 receptors results in antagonism of the catalepsy induced by treatment with a dopamine D2, but not a D1, receptor antagonist. The fact that 5-HTP, in the presence of benserazide and zimeldine, enhanced raclopride-induced catalepsy suggests the possibility of postsynaptic 5-HT receptors acting in opposition to the 5-HT1 and 5-HT2 receptors, as regards extrapyramidal motor functions in the rat.

5-Hydroxytryptophan↗
PubMed1995

Suggestive evidence for a DA D3 receptor-mediated increase in the release of oxytocin in the male rat.

The dopamine (DA) D2/3 receptor agonists quinpirole (0.5-8.0 mg kg-1, s.c.) and 7-OH-DPAT (0.2-3.2 mg kg-1, s.c.), but not the preferential DA D2 receptor agonist bromocriptine (2.0-32.0 mg kg-1, s.c.), produced increased plasma oxytocin levels in the rat. In keeping with their affinity for the DA D2 receptor, all three compounds produced a marked suppression of plasma prolactin levels in their respective dose range. It is suggested that DA D3 receptors are involved in mechanisms regulating oxytocin secretion in the rat.

Animals↗