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S Ahlenius

Publications and source records attributed to S Ahlenius.

At least 91 records · Page 5Linked to original sources
PubMed1991

Photocell measurements of rat motor activity. A contribution to sensitivity and variation in behavioral observations.

A new, photocell-equipped, activity meter is described. The motor activity is observed in a large square, "open field", arena (approximately 0.5 m2) suited for activity observations of rats or other similarly sized animals. Horizontal and vertical activity is recorded at two levels (8 x 8 photocells at each level). Information from each photocell, individually fed into a microcomputer, was used to measure total motor activity, activity in the periphery of the arena, forward locomotion, rearing (total and peripheral), and speed of movement. The equipment has been evaluated by studying the effects of six psychoactive compounds, d-amphetamine, apomorphine, phencyclidine, raclopride, haloperidol, and 8-hydroxy-2-(di-n-propylamino) tetralin. In addition, a graph on the distribution of time intervals between successive photocell beam interruptions, and the within- and between-session habituation in normal animals is provided.

Animals↗
PubMed1991

Behavioural and biochemical effects of subchronic treatment with raclopride in the rat: tolerance and brain monoamine receptor sensitivity.

Male Sprague-Dawley rats were treated with the dopamine (DA) D2 receptor blocking agent raclopride 0.5 or 8.0 mg kg-1 subcutaneously (1.0 and 16.0 mumol kg-1, respectively), twice daily for 21 days. The animals treated with raclopride gained weight at the same rate as saline controls, and gross observation did not indicate any behavioural abnormalities due to the subchronic raclopride treatment. Possible changes in brain DA receptor sensitivity due to prolonged blockade of DA receptors were evaluated in behavioural and biochemical models. There were no effects on locomotor activity, as observed by means of photobeam-equipped activity cages, 24 hr or 72 hr after withdrawal of 0.5 or 8.0 mg kg-1 subchronic raclopride treatment. Twenty-four hr after withdrawal of the raclopride treatment there was an increased post-synaptic DA receptor sensitivity as evidenced by increased behavioural and biochemical responses to apomorphine, and by an attenuated response to acute raclopride treatment, 0.1 mg kg-1. Thus, there was an increase in locomotor activity by the apomorphine treatment in animals pretreated with the 8 mg kg-1 dose, as compared to the response obtained in saline controls. Furthermore, the suppression of locomotor activity in saline controls produced by acute raclopride treatment was dose-dependently antagonized by the raclopride pretreatment and this also applied to the increase in striatal DOPAC levels produced by acute raclopride treatment. Finally, there was an increased DA receptor sensitivity presynaptically as evidenced by an enhanced effect on striatal DOPA levels by apomorphine in rats treated with NSD 1015 and reserpine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of raclopride and haloperidol on spontaneous motor activity and on conditioned avoidance behavior in rats. A comparison of potency, efficacy and time-course of action.

The spontaneous locomotor activity of rats was used as an index of centrally mediated effects of raclopride (CAS 84225-95-6). The results indicate a duration of less than 2 h after s.c. administration of 2 mumol kg-1. In support of a rapid first-pass metabolism in the rat, the effect was considerably weaker after i.p. administration. This difference was further supported by comparing the dose-effect curves after s.c. and i.p. raclopride administration. Haloperidol (CAS 52-86-8) appears to be slightly more potent than raclopride, the estimated ED50 values being 0.15 and 0.24 mumol kg-1 s.c., respectively. Both compounds (s.c. administration) produced a complete suppression of the conditioned avoidance behavior with approximately the same potency. As assessed in the latter situation, the duration of the effects of raclopride is considerably shorter than that of haloperidol.

Animals↗
PubMed1990

Effects of selective dopamine D1 and D2 antagonists on male rat sexual behavior.

The effects of selective dopamine (DA) D1 and D2 antagonists on male rat sexual behavior were investigated. The D1 antagonist (+)SCH-23390, 25-100 micrograms kg-1 s.c. -20 min, and the D2 antagonist raclopride, 0.1-1.6 mg kg-1 s.c., -20 min, decreased both the number of mounts and intromissions preceding ejaculation. No statistically significant effects in the time up to ejaculation or in the time up to the first intromission were noted, whereas both compounds produced a statistically significant increase in the post-ejaculatory interval. The effect can generally be characterized as psychomotor inhibition, and no evidence was obtained for a specific role of DA D1 or D2 receptors in the mediation of male rat sexual behavior.

Animals↗
PubMed1990

Suppression of conditioned avoidance behavior by the local application of (-)sulpiride into the ventral, but not the dorsal, striatum of the rat.

The local application of (-)sulpiride, 200 ng side-1, into the nucleus accumbens produced a suppression of conditioned avoidance behavior in male rats, 10 and 90 min after injection. The decrease in avoidance behavior was accompanied by a decrease in motor activity, as evidenced by changes in the number of intertrial crosses. When injected into the dorsolateral neostriatum, or the amygdala, (-)sulpiride produced a suppression of conditioned avoidance behavior at the 90-min time interval only. Considering diffusion from the injection site, as indicated by an increase in local dopamine turnover [(DO-PAC + HVA) DA-1], the effects obtained in the dorsolateral neostriatum, and possibly also the amygdala, 90 min after injection could be due to diffusion to the nucleus accumbens. The local application of (-)sulpiride into the posterior neostriatum, or into the prefrontal cortex, produced no statistically significant effect on conditioned avoidance behavior 10 or 90 min after injection. It is concluded that the performance of conditioned avoidance behavior in the rat is critically dependent on an intact dopaminergic neurotransmission in the nucleus accumbens or adjacent areas of the ventral striatum.

Amygdala↗
PubMed1990

Effects of 5-HT and 8-OH-DPAT on forebrain monoamine synthesis after local application into the median and dorsal raphe nuclei of the rat.

5-HT (10 and 40 micrograms) and 8-OH-DPAT (1 and 5 micrograms) were locally applied into the dorsal or median raphe nuclei in awake, unrestrained, rats. All animals were also treated with the 5-HTP and DOPA decarboxylase inhibitor NSD-1015, 100 mg kg-1 SC, 30 min before decapitation. 5-HT or 8-OH-DPAT were administered 5 min before NSD-1015. The regional brain in vivo rate of tyrosine and tryptophan hydroxylase activity was estimated by measuring the accumulation of DOPA and 5-HTP. The following brain regions were sampled: neocortex, hippocampus, dorso-lateral neostriatum, ventro-medial neostriatum, nucleus accumbens, olfactory tubercle, globus pallidus, septum and the amygdala. Compared to normal controls, there were small and inconsistent effects on forebrain 5-HTP accumulation by saline injections into the dorsal or the median raphe (an increase in 3 out of 36 experiments), whereas strong effects by the injection procedure were noted on forebrain DOPA accumulation (an increase in 15 out of 36 experiments). Injections of 5-HT (same effect by 10 or 40 micrograms) into the dorsal raphe, produced a decrease in 5-HTP accumulation in all forebrain areas except for the hippocampus and the septum, whereas no effects were seen in any area after median raphe injections. In contrast, 8-OH-DPAT preferentially produced a decrease in forebrain 5-HTP accumulation after median raphe injections and less, but statistically significant effects by dorsal raphe injections. The 8-OH-DPAT injection into the median raphe primarily affected limbic forebrain areas (hippocampus, nucleus accumbens, ventro-medial neostriatum, amygdala and the septum). This dissociation of the effects of 5-HT and 8-OH-DPAT on forebrain 5-HT synthesis after local application into the dorsal or the median raphe strongly supports the contention of heterogeniety in the brain 5-HT receptor population in terms of receptor subtypes and/or receptor regulation.

5-Hydroxytryptophan↗
PubMed1990

Phencyclidine-induced disruption of an aversely motivated two-choice successive discrimination in the rat.

Rats were trained to performed an aversely motivated discriminative task in a shuttle-box. The administration of phencyclidine (PCP), 2 mg kg-1 SC at -20 min, produced disruption of discriminative performance and an increase in intertrial crosses. There were no changes in avoidance performance or in avoidance latency. Pretreatment with haloperidol, 0.1 or 0.2 mg kg-1 SC at -40 min, or remoxipride 8 mg kg-1 IP at -30 min, did not antagonize the PCP-induced disruption of discriminative performance, nor was the PCP-induced increase in number of intertrial crosses antagonized. In fact, there appeared to be a further increase in intertrial crosses, above PCP levels, by haloperidol treatment and this effect was statistically significant after remoxipride treatment. The present results, together with previous observations that also d-amphetamine disrupts discriminative conditioned avoidance behavior, suggest the possibility that this model could be used in the search for new, non-dopaminergic, antipsychotic drugs.

Amphetamine↗
PubMed1990

Loss of discriminative avoidance behavior by local application of kynurenic acid into the nucleus accumbens of the rat.

Male Sprague-Dawley rats, trained to perform a visual discrimination, were administered kynurenic acid, an antagonist of excitatory amino acid receptors, 4.7 micrograms bilaterally into the nucleus accumbens. The performance of the visual discrimination was impaired 15, but not 360, min after administration. In addition, motor activity in the test apparatus was markedly increased by the treatment, whereas no effects were noted when the animals were observed in an open field. The abnormal behavior produced by kynurenic acid has previously been observed after administration of high doses of compounds like d-amphetamine and L-DOPA, and generally discriminative behavior has been shown to be highly dependent on normal impulse mediated release of dopamine in brain. The present results show that this behavior also is dependent on an intact excitatory amino acid neurotransmission.

Animals↗
PubMed1990

Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration in the rat.

The administration of the 5-HT1A agonist 8-OH-DPAT (0.8 mumols kg-1 s.c.-40 min) produced an increase in dopamine (DA) turnover, estimated by the quotient (DOPAC + HVA) DA-1, in the ventral striatum of the rat. No statistically significant effects were obtained in the dorsal striatum. The accumulation of 3-MT in pargyline-treated animals (375 mumols kg-1 s.c.-60 min) was not affected by 8-OH-DPAT treatment (0.15-2.4 mumols kg-1 s.c.-30 min). These findings indicate that 8-OH-DPAT has weak antagonist properties at striatal DA receptors in normal rats. Both the 5-HT1A agonist flesinoxan (0.06-17.8 mumos kg-1 s.c. -50 min) and the mixed 5-HT1 and 5-HT2 agonist 5-MeODMT (1.6-26.0 mumols kg-1 s.c.-50 min) produced a decrease in forebrain 5-HTP accumulation (striatum and neocortex), following decarboxylase inhibition by means of NSD-1015 in reserpine treated rats, indicating stimulation of central 5-HT receptors by these two compounds. At the same time, the DOPA accumulation by the ventral striatum was decreased by flesinoxan and increased by 5-MeODMT treatment. These observations show that, under these conditions, the decrease in DA synthesis is not directly coupled to the decreased 5-HT synthesis produced by flesinoxan, as previously demonstrated for 8-OH-DPAT. Taken together with previous observations, the present results suggest that 8-OH-DPAT, depending on the experimental conditions, is an agonist or antagonist at striatal DA receptors, in all probability due to partial DA receptor agonist properties of the compound.

5-Hydroxytryptophan↗
PubMed1989

Effects of local application of 5-HT into the median and dorsal raphe nuclei on male rat sexual and motor behavior.

The local application of 10 micrograms 5-hydroxytryptamine (5-HT) into the dorsal or median raphe nucleus was found to facilitate male rat sexual behavior, as evidenced by a decrease in time to ejaculation, and in number of intromissions preceding ejaculation. The application of a higher dose, 40 micrograms, at either site, inhibited the initiation of sexual behavior. There was a clear distinction between the motor effects observed after local application of 5-HT into the dorsal or the median raphe nuclei. Injections into the median raphe produced a dose-dependent increase, whereas injections into the dorsal raphe nucleus produced a dose-dependent decrease, in motor activity. Present results suggests an inhibitory and excitatory role of the median and the dorsal raphe serotonergic projections, respectively, as regards motor behavior, whereas projections from both nuclei appear to have an inhibitory role in the mediation of male rat sexual behavior.

Animals↗
PubMed1989

Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat.

Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic L-amino acid decarboxylase by means of NSD-1015, 100 mg kg-1 intraperitoneally. In animals treated with reserpine, 5 mg kg-1 subcutaneously -18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT1A receptor agonist 8-OH-DPAT, 0.15-2.4 mumol kg-1, whereas the partial dopamine D2 receptor agonist (-)3-PPP, 2.5-10.0 mumol kg-1, or the full dopamine D2 receptor agonist quinpirole, 0.05-0.8 mumol kg-1, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 mumol kg-1, but not by (-)pindolol, 8 mumol kg-1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (-)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1989

Evidence for the involvement of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat.

5-Hydroxy-L-tryptophan (5-HTP), 25 mg kg-1 IP, in combination with the peripheral 5-HTP decarboxylase inhibitor benserazide, 25 mg kg-1 IP, and the selective inhibitor of neuronal 5-hydroxytryptamine (5-HT) re-uptake, zimeldine, 10 mg kg-1 IP, suppressed lordosis in ovariectomized female rats, treated with estradiol benzoate (EB) or with EB plus progesterone (P). The suppression of lordosis produced by 5-HTP was antagonized by the beta-receptor blocker (-)pindolol, which also is a selective 5-HT1 receptor antagonist, but not by the 5-HT2 receptor antagonists metitepine or pirenperone, nor by the beta-receptor blocker betaxolol. The EB- or EB plus P-activated lordosis was also suppressed by administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Together, these observations indicate an important role of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat.

5-Hydroxytryptophan↗
PubMed1989

Antagonism by pindolol, but not betaxolol, of 8-OH-DPAT-induced facilitation of male rat sexual behavior.

8-OH-DPAT (0.25 mg/kg s.c.) produced a facilitation of the male rat sexual behavior, characterized by a decrease in the number of intromissions preceding ejaculation and in the time to ejaculation. This facilitation of the sexual behavior was antagonized by administration of the 5-HT and beta-adrenoceptor antagonist pindolol (4 mg/kg i.p.), but not by the selective beta-adrenoceptor antagonist betaxolol (4 mg/kg i.p.). Neither pindolol (2-8 mg/kg), nor betaxolol (2-8 mg/kg), produced any statistically significant effects per se on the male rat sexual behavior, as observed here (mounts, intromissions, ejaculation latency or the post-ejaculatory interval). A higher dose (16 mg/kg) of betaxolol produced a statistically significant reduction in the number of intromissions preceding ejaculation and in the ejaculation latency. The antagonism by pindolol of 8-OH-DPAT-induced effects on male rat sexual behavior suggests an involvement of 5-HT1A receptors in the facilitation of this behavior produced by 8-OH-DPAT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Effects of 8-OH-DPAT on motor activity in the rat.

The administration of 8-OH-DPAT to rats produced a dose-dependent suppression of spontaneous locomotor activity in an open field arena. 8-OH-DPAT was administered in the dose range 12.5-1,600 micrograms.kg-1 SC. Vertical activity ("rearing") was more sensitive to the treatment than horizontal activity ("locomotion"), both in terms of potency and efficacy. The activity along the walls of the open field arena ("peripheral activity") was increased, and the rearing activity was decreased, relative to total horizontal activity and total activity, respectively. There were no effects by 8-OH-DPAT on treadmill locomotion. The rectal temperature was decreased by 8-OH-DPAT administration, not only in animals tested in the open field, but also in animals with an increased body temperature, produced by treadmill locomotion.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Effects of stereoselective 5-HT1A agonists on male rat sexual behavior.

The effects on male rat sexual behavior of some new stereoselective 5-HT agonists, related to 8-OH-DPAT, are presented. It was found that (+)cis-8-hydroxy-1-methyl-2-(di-n-propylamino) tetralin (8-OH-MeDPAT), as well as (-)trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (2-OH-DCPA), and its 3-hydroxy-phenyl analog (3-OH-DCPA), stereoselectively facilitated the male rat sexual behavior, as evidenced by a decrease in the number of intromissions preceding ejaculation, and a shortening of the ejaculation latency. For the former two compounds, studied in further detail, the potency and efficacy appear to be of the same magnitude as previously found for 8-OH-DPAT. The results demonstrate specific 5-HT receptor involvement in the mediation of male rat sexual behavior.

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