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S Ahlenius

Publications and source records attributed to S Ahlenius.

At least 19 recordsLinked to original sources
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 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↗
PubMed1995

Adrenalectomy does not prevent the ability of 8-OH-DPAT to decrease the ejaculatory threshold in male rats.

The present experiments demonstrate that 8-OH-DPAT (0.25 mg/kg SC, - 15 min) produced a decrease in the ejaculatory threshold to the same extent in adrenalectomized male rats as in sham operated controls. Both groups of animals displayed a marked and statistically significant decrease in number of mounts and penile intromissions preceding ejaculation and in the ejaculation latency, as a result of treatment with 8-OH-DPAT. Adrenalectomy per se did not affect any aspect of the male rat's sexual behavior (latency to first intromission, number of mounts or penile intromissions, ejaculation latency or the postejaculatory interval). The surgical removal of the adrenals was verified by measurements of plasma corticosterone levels. It is concluded that well documented effects of 8-OH-DPAT on adrenal secretions do not contribute to its ability to decrease the ejaculatory threshold in male rats.

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

Antagonism of reserpine-induced suppression of spontaneous motor activity by stimulation of 5-HT1A receptors in rats.

The 5-HT1A and the DA D2 receptor agonists 8-OH-DPAT (0.05-3.2 mg kg-1 subcutaneously, -20 min.) and quinpirole (0.08-1.25 mg kg-1 subcutaneously, -20 min.), respectively, both partially antagonized reserpine-induced (5 mg kg-1 subcutaneously, -16 hr) suppression of spontaneous motor activity in the rat. Four different aspects of the spontaneous motor activity were recorded in a photocell-equipped open-field (8 x 8 photocells, 90 mm apart, defining two horizontal planes): locomotor activity (all photocell counts at the lower level); rearing (all photocell counts at the upper level); forward locomotion (the proportion movements across the arena); peripheral activity (the proportion locomotor activity as picked up by the photocell beam closest to the wall, i.e. 25 mm). As defined by these variables, the pattern of activity produced by 8-OH-DPAT or quinpirole were indistinguishable. The effects produced by 8-OH-DPAT were fully antagonized by the 5-HT1 antagonist (-) pindolol (4 mg kg-1 subcutaneously, -30 min.), but not by the DA D2 receptor antagonist raclopride (2 mg kg-1 subcutaneously, -30 min.) nor by the 5-HT2 receptor antagonist ritanserin (2 mg kg-1 subcutaneously, -30 min.), whereas effects produced by quinpirole were fully antagonized by raclopride (2 mg kg-1 subcutaneously, -30 min.). Effects produced by quinpirole, but not 8-OH-DPAT, were potentiated by administration of the DA D1 agonist SKF-38,393 (3 mg kg-1 subcutaneously, -20 min.). It is concluded that effects by 8-OH-DPAT on spontaneous motor activity in the reserpine treated rat primarily are due to stimulation of postsynaptic 5-HT1A receptors.

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

Behavioral and biochemical effects of the dopamine D3 receptor-selective ligand, 7-OH-DPAT, in the normal and the reserpine-treated rat.

In normal rats, the dopamine D3 receptor-selective ligand, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT), produced biphasic effects on spontaneous locomotor activity, i.e. suppression at low doses (0.06-0.25 mumol kg-1 s.c.), followed by a gradual increase in motor activity (1.0-4.0 mumol kg-1). The core temperature was decreased at these latter high doses only. The reserpine-induced (8.2 mumol kg-1 s.c.) increase in neostriatal 3,4-dihydroxyphenylalanine (DOPA) accumulation, following treatment with m-hydroxybenzylhydrazine-(NSD-1015) (475 mumol kg-1 i.p.), was dose dependently antagonized by 7-OH-DPAT in the dose range 0.02-4.0 mumol kg-1. The reserpine-induced suppression of spontaneous locomotor activity, however, was antagonized at higher doses only (1.0-4.0 mumol kg-1). Finally, there were no region-selective effects of 7-OH-DPAT on DOPA accumulation in the neostriatum. Thus, it appears that the dopamine D3 receptor-preferring ligand, 7-OH-DPAT, displays the profile of a dopamine D2 receptor agonist, pre- and postsynaptically.

Analysis of Variance↗
PubMed1994

Antagonism by SCH 23390 of clozapine-induced hypothermia in the rat.

Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.

Amphetamines↗
PubMed1994

Time course for synchronization of spontaneous locomotor activity in the rat following reversal of the daylight (12:12 h) cycle.

The present results demonstrate that 5-7 days on a reversed light-dark cycle (12:12 h) is sufficient for the synchronization of spontaneous locomotor activity with the new circadian rhythm in rats. Once established, the circadian rhythm is stable for at least 3 days under constant illumination conditions. Reversal of the light-dark cycle appears to be both a reliable and practical procedure in everyday laboratory work.

Animals↗
PubMed1994

Evidence for specific interactions between 5-HT1A and dopamine D2 receptor mechanisms in the mediation of extrapyramidal motor functions in the rat.

Administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg kg-1 SC) completely antagonised the catalepsy produced by the dopamine (DA) D2 receptor antagonist raclopride (16 mg kg-1 SC). This effect by 8-OH-DPAT was in turn completely antagonised by treatment with the new 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin [(S)-UH-301] (3.5 mg kg-1 SC), but not by the mixed 5-HT1 receptor/beta-adrenoceptor antagonist (-)pindolol (2.0 mg kg-1 SC). The failure by (-)pindolol to antagonise the effects of 8-OH-DPAT on raclopride-induced catalepsy could be due to its beta-receptor-blocking properties, since by themselves both (-)pindolol and the selective beta-adrenoceptor antagonist betaxolol (4 mg kg-1 SC) at least partially antagonised the raclopride-induced catalepsy. The present results provide further support for specific interactions between 5-HT1A and DA D2 receptor mechanisms in the mediation of extrapyramidal motor functions in the rat.

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

High doses of oxytocin cause sedation and low doses cause an anxiolytic-like effect in male rats.

The aim of the present investigation was to explore dose relationships for effects of oxytocin on spontaneous motor activity in the rat. Oxytocin in doses from 1-1000 micrograms/kg was given SC to male Sprague-Dawley rats, and spontaneous motor behavior was measured by means of photocell-operated open-field observations. In the rats treated with low doses of oxytocin (1-4 micrograms/kg), there was a decrease in peripheral locomotor activity. With increasing doses (250-1000 micrograms/kg), there were clear signs of sedative effects as indicated by a suppression of locomotor activity and rearing. The time course for the effect of oxytocin on peripheral activity (1 microgram/kg) and rearing (1 mg/kg) was tested. A maximal effect was obtained within 1 h and, thereafter, the behavior gradually returned to normal within 24 h. This spectrum of effects caused by oxytocin was similar to that of midazolam but different from that induced by raclopride.

Animals↗
PubMed1994

A new computer-assisted two-way avoidance conditioning equipment for rats: behavioral and pharmacological validation.

A new PC-controlled two-way avoidance conditioning equipment for rats is described. The position of the rat within the two-compartment shuttle-box is monitored by means of 4 + 4 horizontal photocell beams. Experimental conditions and procedures, such as CS-UCS interval, photocell operations, shock strength, and so on, can conveniently be preset by the experimenter. The successful operation of the shuttle-box is evidenced by rapid and efficient acquisition of the avoidance behavior, and approximately 100% median avoidance performance was obtained within 5 successive days of training (20-25 trials per day). In a separate experiment, different groups of rats received avoidance training (0-5 sessions) at 8 weeks of age, and a retention test was performed at 14 weeks of age. The correlation between acquisition and retention avoidance performance was weak (r = 0.33, NS), and performance during the acquisition process appears to be a poor predictor of final performance. As expected, a number of dopamine (DA) receptor blocking agents (DA D1 and/or D2 selective) produced a selective suppression of the avoidance behavior, that is, the suppression of avoidance responding was matched by a corresponding increase in escape responding (with no escape failures).

Animals↗
PubMed1993

Effects of exposure to an estrous female on forebrain monoaminergic neurotransmission in the non-copulating male rat.

Regional changes in the rate of brain monoamine synthesis were monitored in male rats exposed to, but prevented from physical contact with, an estrous or an ovariectomized female. The in vivo rate of tyrosine and tryptophan hydroxylase activities were estimated by measuring the accumulation of DOPA and 5-HTP following inhibition of cerebral aromatic L-amino acid decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015) treatment (100 mg/kg i.p.). 5 min upon NSD-1015 treatment, the males were exposed to an intact estrous female or an ovariectomized female for 20 min before decapitation and brain dissections. Exposure to an estrous female produced an increased rate of tyrosine and tryptophan hydroxylase activity in the medial prefrontal cortex, the dorso-lateral neostriatum and in the ventral neostriatum, in comparison with home-cage controls. By the same comparison, exposure to an ovariectomized female resulted in an increased rate of tyrosine hydroxylase activity in the medial prefrontal cortex, but not in the neostriatal areas, whereas tryptophan hydroxylase activity was unaffected. Finally, exposure to the empty test cage, with no stimulus females present, did not produce any statistically significant changes in the rate of tyrosine or tryptophan hydroxylase activity in any of the brain areas sampled. Taken together with recent findings from this laboratory, the present results demonstrate that the level of sexual motivation brought about by the olfactory, auditory and/or visual stimulation of a receptive female is associated with an increased demand on catecholamine and 5-hydroxytryptamine synthesis in the limbic forebrain of the male rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1993

Evidence for specific involvement of dopamine D1 and D2 receptors in the regulation of body temperature in the rat.

Administration of the selective dopamine D1 and D2 receptor agonists, A 68930 (0.9-60.0 mumol kg-1 s.c.) and quinpirole (0.1-6.0 mumol kg-1 s.c.), produced a dose-dependent decrease in core temperature in the rat. The hypothermia induced by quinpirole (1.5 mumol kg-1) was antagonized by pretreatment with the selective dopamine D2 receptor antagonist, raclopride (1.6 mumol kg-1 s.c.), but not by the dopamine D1 receptor antagonist, SCH 23390 (0.3 mumol kg-1 s.c.), whereas the hypothermia induced by A 68930 (3.8 mumol kg-1) was antagonized by SCH 23390 (0.3 mumol kg-1), but not by raclopride (1.6 mumol kg-1). Together, these results suggest that both dopamine D1 and D2 receptors are specifically involved in the regulation of body temperature in the rat.

Animals↗
PubMed1993

Potency mismatch for behavioral and biochemical effects by dopamine receptor antagonists: implications for the mechanism of action of clozapine.

Clozapine (3.8-60.0 mumol kg-1) did not produce any alterations in DOPA accumulation (following inhibition of cerebral aromatic L-amino acid decarboxylase) in the prefrontal cortex or in three regions of the neostriatum, i.e. the ventral, the dorso-lateral and the posterior regions, in the rat. In contrast, clozapine produced a reduction in the 5-HTP accumulation in all these brain areas, except for the prefrontal cortex. Raclopride (0.08-20.0 mumol kg-1) produced a marked increase in DOPA accumulation in all four brain regions and an increase in 5-HTP accumulation in the dorso-lateral neostriatum (2.5-20.0 mumol kg-1), but not in the other forebrain regions. Treatment with SCH-23390 (0.4-1.6 mumol kg-1) resulted in increased DOPA accumulation in the ventral and posterior parts of the neostriatum. No other changes in the DOPA or 5-HTP accumulation were seen with SCH-23390. Considering the doses of these three compounds needed for suppression of conditioned avoidance behavior and for the induction of cataleptic rigidity, it is concluded that raclopride produces an increased DA synthesis at much lower doses than those needed for behavioral effects. In contrast, the behavioral effects of SCH-23390 or clozapine precedes effects on brain DA synthesis on the dose-effect curve. In fact, the only biochemical effect of clozapine, which was observed in low, yet behaviorally active doses, was a decrease in forebrain 5-HTP accumulation. In conclusion, the present results demonstrate a mismatch, in different directions for raclopride and SCH-23390, as regards to the doses needed to produce effects on brain dopamine synthesis and on behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Brain monoaminergic neurotransmission in the mediation of lordosis behavior in the female rat.

The present paper reviews recent pharmacological evidence indicating an important role for central monoaminergic neurotransmission in the mediation of lordosis behavior in the female rat. Following the initial observations by Meyerson and his colleagues in the early 1960s, demonstrating an inhibitory serotonergic mechanism, continued studies have identified 5-hydroxytryptamine (5-HT) 5-HT1A receptors to be of particular importance. Stimulation of central 5-HT2 receptors appear to have an opposite role, i.e. facilitating the elicitation of the lordosis response. As regards brain dopaminergic neurotransmission, it appears that brain dopamine (DA) D2 receptors mediate an inhibitory effect on the lordosis behavior, whereas no distinct role has been ascribed to DA D1 receptors. The serotonergic and the dopaminergic mechanisms can be manipulated independently, perhaps indicating the operation of parallel mechanisms. Most of the evidence presented above has been obtained in experiments on ovariectomized female rats primed with subthreshold doses of estrogen. It appears, however, that at least the inhibitory effects mediated by serotonergic neurotransmission are not dependent on the presence of progesterone.

Animals↗