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S Ahlenius

Publications and source records attributed to S Ahlenius.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1993

Effects of 5-HT1A receptor agonists on patterns of rat motor activity in relation to effects on forebrain monoamine synthesis.

The effects of the 5-HT1A receptor agonists 8-OH-DPAT (0.15-2.5 mumol kg-1 subcutaneously), flesinoxan (0.6-10.0 mumol kg-1 subcutaneously) and buspirone (1.9-30.0 mumol kg-1 subcutaneously) on spontaneous motor activity in male Sprague-Dawley rats was examined in a photocell-equipped open-field arena. Following motor activity observations, the cerebral aromatic L-amino acid decarboxylase inhibitor NSD-1015 (100 mg kg-1 intraperitoneally) was administered and 30 min. later the animals were decapitated for subsequent analysis of the accumulated forebrain DOPA and 5-HTP levels, as an estimate of the rate of monoamine synthesis. 8-OH-DPAT and flesinoxan produced a similar and characteristic pattern of changes of the spontaneous motor activity in normal animals i.e. a moderate decrease in locomotor activity, a marked suppression of rearing and an increase in the relative amount of forward locomotion and of activity in the periphery of the open-field arena. This behavioural profile was closely related to a decrease in forebrain 5-HTP accumulation, indicating 5-HT receptor stimulation. In agreement with these observations buspirone also produced an increase in peripheral activity and a suppression of rearing. In contrast to effects by 8-OH-DPAT and flesinoxan, however, buspirone produced a further reduction of locomotor activity and reduced the forward locomotion. This difference in behavioural profile between buspirone and the other two compounds is probably explained by its DA receptor blocking properties, as indicated by an increased DOPA accumulation in the neostriatum. At least partially, 8-OH-DPAT, flesinoxan and buspirone, all antagonized reserpine-induced (5 mg kg-1 subcutaneously--16 hr) suppression of locomotor activity. This stimulation of locomotor activity in reserpine-treated rats is in all probability related to 5-HT1A receptor stimulation since concomitant DA D2 receptor blockade, in the case of buspirone, did not markedly affect this behavioural response.

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

Stimulation of brain dopamine autoreceptors by remoxipride administration in reserpine-treated male rats.

Male Sprague-Dawley rats were treated subcutaneously with reserpine (5 mg kg-1, -18 h) and with the aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine) (100 mg kg-1 -30 min). Remoxipride 0.8, 3.2 or 12.8 mg kg-1 was administered subcutaneously at -50 min. Immediately following decapitation (0 h), the ventral striatum and the anterior neocortex were dissected. Dopa and 5-hydroxytryptophan accumulation in these brain areas were analysed by HPLC with electrochemical detection. Reserpine produced a marked increase in striatal and neocortical dopa accumulation, in comparison with glucose vehicle + NSD-1015-treated controls, and this increase was dose-dependently antagonized by remoxipride treatment. Thus, together with demonstrated dopamine receptor antagonist actions in intact animals, remoxipride behaves as a mixed dopamine receptor agonist-antagonist. Such properties could contribute to the favourable endocrine and extrapyramidal side effect profile of remoxipride as an antipsychotic agent.

5-Hydroxytryptophan↗
PubMed1992

Mixed agonist-antagonist properties of umespirone at neostriatal dopamine receptors in relation to its behavioral effects in the rat.

In normal rats treated with the inhibitor of cerebral decarboxylase, NSD-1015 (100 mg kg-1 i.p.), umespirone (1.9-30.0 mumol kg-1 s.c.) produced an increase in neostriatal DOPA (dihydroxyphenylalanine) accumulation, whereas decreased DOPA accumulation was obtained in reserpine-pretreated (5 mg kg-1 s.c., -18 h) animals. The latter effect was statistically significant only in the ventral, limbic, portion of the neostriatum. Neostriatal 5-hydroxytryptophan (5-HTP) accumulation was decreased in the reserpine-treated animals but not in normal controls. DOPA accumulation in the neocortex was not affected by umespirone treatment in either preparation, whereas 5-HTP accumulation was decreased in the reserpine-treated animals. Spontaneous locomotor activity was suppressed by umespirone at doses that did not affect treadmill locomotion (7.9-31.2 mumol kg-1 s.c., -30 min), and there were no signs of catalepsy at doses ranging from 31.2-249.6 mumol kg-1 s.c. up to 2 h after injection. Thus, umespirone behaves as a mixed dopamine receptor agonist/antagonist and also displays 5-HT receptor agonist properties. This biochemical profile was associated with sedation, as observed in the open-field, at doses which did not affect treadmill locomotion or induced catalepsy.

5-Hydroxytryptophan↗
PubMed1992

Stimulation of 5-HT1A and 5-HT1B receptors in brain regions and its effects on male rat sexual behaviour.

In the present series of experiments we compared the effect of injecting serotonin (40 micrograms/cannula), the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5.0 micrograms/cannula), and the 5-HT1B/C agonist, trifluoromethyl-phenyl-piperazine (TFMPP) (1.0 micrograms/cannula), into the preoptic area, the nucleus accumbens and the nucleus raphe dorsalis. The dose injected was selected on the basis of dose-response curves. Injection of serotonin and TFMPP into the medial preoptic area and nucleus accumbens resulted in an inhibition of male sexual behaviour, as evidenced by an increase in the number of mounts and a prolongation of the ejaculation latency. Injection of 8-OH-DPAT into these brain areas facilitated copulatory behaviour as evidenced by a reduction in the number of mounts, intromissions and ejaculation latency. Administration of these compounds into the nucleus raphe dorsalis produced no effect, except for a prolongation of the intromission latency after serotonin. These results would suggest that at least some of the 5-HT1A receptors involved in the facilitation of male sexual behaviour are located postsynaptically in limbic brain areas that regulate male sexual behaviour. On the basis of the similarities between the inhibitory effects of serotonin and TFMPP, the present results further support the idea that endogenous serotonin acts via the stimulation of 5-HT1B receptors to inhibit male sexual behaviour.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Effects of the local application of 3-PPP and sulpiride enantiomers into the nucleus accumbens or into the ventral tegmental area on rat locomotor activity: evidence for the functional importance of somatodendritic autoreceptors.

The present series of experiments was performed in order to determine the relative role of presynaptic and somato-dendritic autoreceptors for the sedative effects produced by systemically administered dopaminergic agonists. Thus, the effects of intracerebral administration of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), or sulpiride, enantiomers on spontaneous locomotor activity was investigated in rats. It was found that the local application of (-)3-PPP, but not (+)3-PPP, into the nucleus accumbens (1.25-80.0 micrograms, bilaterally) produced a suppression of the locomotor activity, whereas the local application of the two enantiomers into the ventral tegmental area resulted in a suppression of the locomotor activity in the same dose range. Thus, the full dopamine D2 agonist (+)3-PPP produced suppression of locomotor activity only after local application into the somato-dendritic region, suggesting that in terminal areas postsynaptic receptor stimulation effectively counterbalanced the functional consequences of presynaptic receptor stimulation. The sulpiride enantiomers both produced a suppression of locomotor activity after local application into the accumbens (0.2-5.0 micrograms, bilaterally). In the ventral tegmental area, however, (-)sulpiride administration (0.2-5.0 micrograms, bilaterally) resulted in an increased locomotion, whereas the (+)enantiomer produced no effect or, at the highest dose (5.0 micrograms), a suppression of the locomotor activity. These observations indicate that for a dopamine D2 antagonist, the postsynaptic receptor blockade in the terminal region, resulting in behavioral suppression, not only counteract compensatory effects produced via the presynaptic receptor in this region, but also to a great extent overshadow the functional consequences of somatodendritic autoreceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Relationship between brain levels of 3-(3-hydroxyphenyl)-N-n-propylpiperidine HCl enantiomers and effects on locomotor activity in rats.

After s.c. administration of 3-(3-hydroxyphenyl)-N-n-propylpiperidine HCl (3-PPP) to rats, plasma and brain levels were monitored in relation to the amount of spontaneous locomotor activity. Based on time-course relationships, concentration-effect curves were elaborated after administration of (-)3-PPP and (+)3-PPP in the dose range of 1 to 256 mumol.kg-1. Both enantiomers were readily absorbed and distributed, as evidenced by a close correlation between brain and plasma levels, brain levels being 7 to 9 times higher than those found in plasma. Plasma half-lives were 25 and 32 min for (-)3-PPP and (+)3-PPP, respectively. Plotting brain concentrations of (-)3-PPP against locomotor activity resulted in a good fit to a declining two-phase curve, in all probability reflecting preferential actions at pre- and postsynaptic dopamine receptors, respectively. These two underlying mechanisms could also be identified from the biphasic effects produced by (+)3-PPP on locomotor activity: suppression followed by stimulation, respectively. Together, these observations provide further support for the contention that at low doses, both enantiomers have sedative actions due to stimulation of inhibitory autoreceptors. With increasing doses, however, a postsynaptic receptor blockade will predominate for a partial agonist like (-)3-PPP, producing suppression of locomotion, whereas the full agonist, (+)3-PPP, will produce behavioral activation due to stimulation of postsynaptic receptors.

Animals↗
PubMed1991

Effects of sexual interactions on the in vivo rate of monoamine synthesis in forebrain regions of the male rat.

The effects of heterosexual interactions on the in vivo rate of regional brain monoamine synthesis were examined in the male rat. To this end, the animals were administered an inhibitor of cerebral aromatic L-amino acid decarboxylase, NSD-1015 (100 mg.kg-1 i.p.), and regional brain DOPA and 5-HTP accumulation, over a 15-35 min period of sexual interaction, was compared with the DOPA or 5-HTP accumulation in time-matched home cage controls. Using the DOPA and 5-HTP accumulation as an estimate for the rate of tyrosine and tryptophan hydroxylase activity, respectively, the present results demonstrate: (1) an increased demand on catecholamine synthesis in the neocortex, the amygdala and in the septal area; and (2) an increased dopamine and serotonin synthesis in the ventral striatum (excluding the olfactory tubercle), and in the dorsal striatum.

5-Hydroxytryptophan↗
PubMed1991

Behavioral and biochemical effects of the 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT in the rat.

The 5-HT1A receptor agonists flesinoxan (0.2-3.2 mg kg-1 s.c.) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.025-0.4 mg kg-1 s.c.) produced (1) a dose-dependent facilitation of male rat ejaculatory behavior and (2) characteristic, dose-dependent effects on spontaneous motor activity. Thus, total locomotor activity and rearing activity were decreased. However, forward locomotion and peripheral locomotion were increased relative to the total horizontal activity. Furthermore, (3) 5-HTP accumulation, after inhibition of cerebral decarboxylase, was dose dependently decreased by both compounds in the ventral striatum and in the prefrontal cortex. There was a statistically significant decrease in DOPA accumulation in the ventral striatum after administration of a high dose of flesinoxan (3.2 mg kg-1), and a tendency for 8-OH-DPAT to produce the same effect. The efficacy of the compounds to affect male rat sexual behavior, spontaneous motor activity in the open-field and forebrain 5-HT synthesis was approximately the same, whereas flesinoxan was about an order of magnitude less potent than 8-OH-DPAT.

5-Hydroxytryptophan↗
PubMed1991

Quinpirole--a 5-HT receptor antagonist?

The rate of brain monoamine synthesis was estimated in the rat by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) following inhibition of cerebral aromatic amino acid decarboxylase by NSD-1015 (475 mumol/kg, i.p., 30 min before decapitation). As expected, pretreatment with reserpine, (8.2 mumol/kg, s.c., -18 h) produced a marked and statistically significant increase in the DOPA accumulation in the ventral striatum and in the neocortex, whereas only minor changes were noted in 5-HTP accumulation in the same brain areas. The administration of terguride or quinpirole (30 mumol/kg, s.c., -65 min) resulted in both cases in an antagonism of the reserpine-induced increase in the DOPA accumulation. The effect was less marked in the neocortex than in the ventral striatum, but there was no difference between the effects produced by either compound. In contrast, the two drugs produced opposite effects on the 5-HTP accumulation in the ventral striatum as well as in the neocortex. Thus, there was a decrease and an increase in the 5-HTP accumulation by terguride and quinpirole administration, respectively. Together the results suggest that, in the reserpine treated rat, both terguride and quinpirole to the same degree stimulate dopamine receptors in the ventral striatum and noradrenaline receptors in the neocortex. To the extent that serotonin receptors in these two brain areas mediate the effects on 5-HTP accumulation of terguride and quinpirole, respectively, these receptors appear differently affected by the two compounds: stimulation by terguride and blockade by quinpirole.

Animals↗
PubMed1991

Region-selective inhibition of male rat sexual behavior and motor performance by localized forebrain 5-HT injections: a comparison with effects produced by 8-OH-DPAT.

The local application of 5-HT (0-40 micrograms side-1) into the nucleus accumbens was found to inhibit male rat sexual behavior, as evidenced by an increase in number of mounts and intromissions preceding ejaculation and in time to ejaculation. There were no effects on male rat sexual behavior after similar 5-HT injections into other striatal areas, including the dorsolateral, the ventromedial and the posterior neostriatum, as well as the olfactory tubercle. The same groups of animals were also scored for motor activity and body posture after the injection of 5-HT, and only animals injected into the nucleus accumbens showed a statistically significant decrease in motor activity and an increase in the display of a flat body posture. 8-OH-DPAT (0-5 micrograms side-1), injected into the nucleus accumbens, produced a facilitation of the male rat sexual behavior, as evidenced by a decrease in number of mounts and intromissions to ejaculation, as well as in the postejaculatory interval. 8-OH-DPAT injections into the nucleus accumbens produced a decrease in motor activity and an increase in the per cent animals with a flat body posture. Injections into the olfactory tubercle had no effects on the sexual behavior or on the motor activity, whereas the per cent flat body posture was increased. Local application of 8-OH-DPAT (0-5 micrograms) into the median raphe nucleus, facilitated male rat sexual behavior, as evidenced by a decrease in number of intromissions preceding ejaculation and in time to ejaculation. The same doses of 8-OH-DPAT injected into the dorsal raphe had no effects on the sexual behavior. In an additional experiment, 3 groups of animals were injected with 5-HT (40 micrograms) or 8-OH-DPAT (5 micrograms) into the nucleus accumbens, the dorsal and the median raphe nuclei and thereafter observed for treadmill performance. No statistically significant effects were found after injections in any of these brain areas. The present results strongly suggest an inhibitory role of ventral forebrain 5-HT in the mediation of male rat sexual behavior. The facilitation produced by 8-OH-DPAT is possibly due to a blockade of 5-HT2 receptors. Facilitation by 8-OH-DPAT of the male rat copulatory performance after median raphe injections is probably due to stimulation of 5-HT1A autoreceptors in this brainstem region. In contrast to their opposite effects on sexual behavior, both compounds produced a decrease in motor activity and an increased display of flat body posture after accumbens injections.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsy.

The administration of the 5-HT1A agonist 8-OH-DPAT, 0.1 mg kg-1 sc-20 min, produced a moderate suppression of conditioned avoidance behavior (60% of controls) in the rat. This effect, however, was not seen after administration of higher doses, 0.4 and 1.6 mg kg-1 sc. The number of intertrial crosses were not affected by the lower dose but significantly increased by administration of the two higher doses of 8-OH-DPAT. The dopamine D2 receptor blocking agent raclopride, 0.05 mg kg-1, by itself did not suppress the avoidance behavior, but in combination with 8-OH-DPAT produced suppression of avoidance behavior (30% of controls) as well as intertrial crosses. Open field locomotor activity was suppressed by raclopride, 0.1 mg kg-1 sc, or by 8-OH-DPAT, 0.1 mg kg-1 sc. The combined treatment produced a further suppression of locomotor activity and a marked increase in "immobility" (stationary movements). Treadmill locomotion, however, was not affected by either compound by itself, whereas the combined treatment impaired treadmill performance. Suppression of treadmill performance by a higher dose of raclopride, 0.4 mg kg-1 sc, was not altered by the additional treatment with 8-OH-DPAT, 0.1 mg kg-1. In contrast to the additive effects of 8-OH-DPAT and raclopride on conditioned avoidance behavior, open field locomotion and treadmill performance, the catalepsy produced by raclopride, 16 mg kg-1 was completely antagonised by treatment with 8-OH-DPAT 0.1 mg kg-1. Taken together, the present findings demonstrate strong interactions between a 5-HT agonist and a DA D2 antagonist on some critical tests for antipsychotic-like actions and extrapyramidal motor effects in rats, and suggest new possibilities in the search for new antipsychotic drugs with higher clinical efficacy and less extrapyramidal side effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Opposite effects of 5-methoxy-N,N-di-methyl-tryptamine and 5-hydroxytryptophan on male rat sexual behavior.

The administration of 5-methoxy-N,N-di-methyl-tryptamine (5-MeODMT), O-2.0 mg.kg-1 SC -15 min, produced a dose-dependent facilitation of the male rat sexual behavior, as evidenced by a decrease in the number of intromissions to ejaculation and in the ejaculation latency. The effects produced by 5-MeODMT (1 mg.kg-1) were antagonized by pindolol (4 mg.kg-1 SC -30 min), but not pirenperone (0.25 mg.kg-1 SC -30 min) or metergoline (1 mg.kg-1 SC -30 min), administration. As expected, 5-HTP (25 mg.kg-1 SC -60 min) produced an increased number of mounts and intromissions to ejaculation and an increase in the ejaculation latency in benserazide (25 mg.kg-1 SC -90 min) pretreated animals. Pindolol (4 mg.kg-1) by itself produced the same effects as seen after 5-HTP administration, and the combination of these compounds produced additive effects. Betaxolol (8 mg.kg-1 SC -30 min) had no effects of its own and did not interact with 5-HTP. The results suggest that stimulation of brain 5-HT1 or 5-HT2 receptors produces facilitation and inhibition, respectively, of the male rat sexual behavior.

5-Hydroxytryptophan↗