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C L Broekkamp

Publications and source records attributed to C L Broekkamp.

At least 37 records · Page 2Linked to original sources
PubMed1991

Age dependence of 5-methoxytryptamine-induced hindlimb scratching in rats.

The influence of age on hindlimb scratching induced in rats by the serotonin agonist, 5-methoxytryptamine (5-MeOT), was studied. The 5-MeOT-induced scratching was strongest in 30-day-old rats and least in 90-day-old rats. Sex hormones do not play a role in these differences since treatment of young male rats with testosterone propionate did not change the scratching response. The same age dependence was found for female rats as for males.

5-Methoxytryptamine↗
PubMed1991

A peripheral 5-HT1D-like receptor involved in serotonergic induced hindlimb scratching in rats.

The pharmacological characteristics of hindlimb scratching induced by serotonergic compounds were studied. We conclude that hindlimb scratching induced by serotonergic compounds is mediated by a serotonin1D (5-HT1D) or 5-HT1D-like receptor outside the blood-brain barrier because hindlimb scratching could be induced by s.c. injection of 5-methoxytryptamine (5-MeOT), 5-carboxamidotryptamine (5-CT), bufotenine, 5-hydroxytryptamine (5-HT) and tryptamine. These compounds have high affinity for 5-HT1A and 5-HT1D receptors. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C receptor agonist MK 212, and the mixed 5-HT1C/5-HT2 receptor agonists (dl)-1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and quipazine did not induce hindlimb scratching. Rather, the latter compounds attenuated 5-MeOT-induced hindlimb scratching. The 5-HT releasing compounds fenfluramine and p-chloroamphetamine (PCA) inhibited whereas the 5-HT re-uptake inhibitors fluvoxamine and indalpine potentiated 5-MeOT-induced hindlimb scratching. 5-MeOT-induced hindlimb scratching could be inhibited dose dependently by the alpha 2-adrenoceptor blockers yohimbine and rauwolsince, which also have high affinity for 5-HT1D receptors, whereas the alpha 2-adrenoceptor blocker piperoxan only weakly counteracted hindlimb scratching. Haloperidol, apomorphine, morphine, clonidine and methiothepin strongly attenuated hindlimb scratching, atropine, naloxone and ICS 205930 attenuated it weakly whereas domperidone, methylatropine and mepyramine were inactive in doses up to 10 mg/kg. Hindlimb scratching induced by 5-MeOT was potentiated by the 5-HT receptor antagonists metergoline, methysergide, mesulergine, mianserin, ritanserin and xylamidine. Hindlimb scratching was not induced by i.c.v. injection of 5-MeOT.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxytryptamine↗
PubMed1991

Drugs acting at D-1 and D-2 dopamine receptors induce identical purposeless chewing in rats which can be differentiated by cholinergic manipulation.

Purposeless chewing in rats was dose dependently increased by acute administration of the dopamine D-1 receptor agonist SKF 38393 (5-20 mg/kg), the D-2 receptor antagonist sulpiride (10-100 mg/kg) and the D-2 receptor agonist quinpirole (0.05-0.25 mg/kg). Only high doses of the D-1 receptor antagonist SCH 23390 (1 and 5 mg/kg) induced purposeless chewing. SCH 23390 (0.05 mg/kg) blocked SKF 38393 (20 mg/kg)-induced purposeless chewing, but had no effect on the purposeless chewing induced by sulpiride (100 mg/kg) or quinpirole (0.1 mg/kg). A dose of SKF 38393 (5 mg/kg) which did not itself induce chewing, potentiated the increase in purposeless chewing observed after administration of sulpiride (100 mg/kg). Administration of SKF 38393 (20 mg/kg) and quinpirole (0.1 mg/kg) did not induce purposeless chewing but stereotyped licking was observed. Administration of sulpiride (100 mg/kg) with quinpirole (0.1 mg/kg) produced an incidence of purposeless chewing not different from that observed when either compound was administered alone. Acute administration of the cholinergic agonist pilocarpine (0.5-4.0 mg/kg) or the cholinesterase inhibitor physostigmine (0.05-0.2 mg/kg) increased the frequency of purposeless chewing in rats. Co-administration of pilocarpine (0.5 mg/kg) with sulpiride (100 mg/kg) increased the frequency of purposeless chewing above that seen when either compound was administered alone. Co-administration of pilocarpine (0.5 mg/kg) with SKF 38393 (20 mg/kg) increased the frequency of purposeless chewing in an additive manner. Co-administration of physostigmine (0.1 mg/kg) with sulpiride (100 mg/kg) but not SKF 38393 (20 mg/kg), increased the frequency of purposeless chewing above that observed when either compound was administered alone. Quinpirole (0.1 mg/kg)-induced purposeless chewing was not affected by co-administration with either pilocarpine (0.5 mg/kg) or physostigmine (0.1 mg/kg). The anticholinergic agent scopolamine (0.1 mg/kg) blocked the purposeless chewing induced by either SKF 38393 (20 mg/kg) or sulpiride (100 mg/kg), but had no effect on the purposeless chewing induced by quinpirole (0.1 mg/kg). Contrary to previous reports, acute manipulation of D-1 or D-2 receptor function can both enhance purposeless chewing behaviour in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Attenuation of 5-HT1A and 5-HT2 but not 5-HT1C receptor mediated behaviour in rats following chronic treatment with 5-HT receptor agonists, antagonists or anti-depressants.

The effects of chronic (10 days) treatment with serotonin (5-HT) receptor agonists on 5-HT1A receptor mediated lower lip retraction (LLR), 5-HT1C receptor mediated penile erections (PE) or 5-HT2 receptor mediated head shakes (HS) were studied in rats. It was found that the 5-HT1A and 5-HT2 receptor mediated behaviour could be attenuated after chronic treatment, whereas 5-HT1C receptor mediated behaviour remained unchanged. The ED50 for the 5-HT1A receptor mediated, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)-induced LLR showed an increase from 0.07 mg/kg in placebo pretreated rats to 0.13 in 8-OH-DPAT (1 mg/kg/day) pretreated rats. The number of 5-HT2 receptor mediated (+/-)-1-2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.46 and 1 mg/kg)-induced HS was significantly reduced (67% and 50%, respectively) after 10 days' pretreatment with DOI (1 mg/kg/day). In the same animals the number of 5-HT1C receptor mediated PE was increased. Ten days' pretreatment with MK 212 (0.46 mg/kg/day) failed to affect MK 212 (0.22 and 0.46 mg/kg)-induced PE. In addition, the effects of chronic treatment with some antidepressants were studied. The monoamine oxidase (MAO) inhibitor tranylcypromine (4 mg/kg/day) given for 10 days caused an increase in the ED50 for 8-OH-DPAT induced LLR (ED50 values were 0.06 and 0.14 mg/kg, respectively, in placebo--and tranylcypromine--pretreated rats) and attenuated MK 212 (0.22 and 0.46 mg/kg)-induced PE. Chronic treatment with mianserin (10 mg/kg/day), a tetracyclic antidepressant with 5-HT1C and 5-HT2 receptor antagonistic properties, did not change PE induced by MK 212, but caused an increase of PE induced by DOI and a decrease of DOI-induced HS. Ten days' pretreatment with the 5-HT re-uptake inhibitor Org 6997 (5 mg/kg/day) had no effect on MK 212-induced PE. The results demonstrate that 5-HT1A and 5-HT2 but not 5-HT1C receptor mediated behaviour can be attenuated by chronic treatment with agonists for these receptors. The 5-HT1C receptor mediated behaviour remains unchanged in response to chronic agonist treatment. Chronic treatment with antidepressants have differential effect on these behaviours. The possible implication for the mechanism of action of antidepressants is discussed.

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

Depletion of brain serotonin differently affects behaviors induced by 5HT1A, 5HT1C, and 5HT2 receptor activation in rats.

5-hydroxytryptamine (5HT)-depleted rats were subjected to behavioral experiments in which the response to activation of 5HT1A, 5HT1c, and 5HT2 receptor subtypes was measured. Depletion of 5HT was produced by unilateral intracerebroventricular injection of 5,7-dihydroxytryptamine (100 micrograms/rat) or by systemic injection of p-chlorophenylalanine (150 mg/kg injected intraperitoneally 72, 48, and 24 h before the test). The dose-response curve of the 5HT1A-mediated, 8-hydroxy-2-(di-n-propylamino)tetralin (0.022-0.46 mg/kg)-induced lower lip retraction was not changed after depletion, nor was the dose-response curve of the 5HT2 receptor-mediated (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (0.046-1.0 mg/kg)-induced head shake response. The dose-response curve for penile erections, a 5HT1c receptor-mediated response after mCPP (0.1-1.0 mg/kg), a direct 5HT1c agonist, is shifted to the left after 5HT depletion, whereas the response to indirect activation of the 5HT1c receptor with the 5HT reuptake inhibitors citalopram (2.2-4.6 mg/kg) and paroxetine (0.22-2.2 mg/kg) was inhibited after 5HT depletion. These results suggest that 5HT1c receptors are more subject to denervation supersensitivity than 5HT1A and 5HT2 receptors. This lesion model may be useful to discriminate behaviorally between direct and indirect activation of the 5HT1c receptor.

5,7-Dihydroxytryptamine↗
PubMed1990

Antagonism of 8-OH-DPAT-induced behaviour in rats.

Selective activation of the 5-HT1A receptor induces lower lip retraction (LLR) in rats. 8-Hydroxy-dipropylamino tetralin (8-OH-DPAT)-induced LLR could not be antagonised by the 5-HT antagonists methysergide, metergoline or mesulergine. In fact, some 5-HT antagonists induced LLR. However, 8-OH-DPAT-induced LLR could be antagonised by pindolol, spiperone, spiroxatrine and NAN-190, but not by the beta 1-adrenoceptor antagonist metoprolol, the beta 2-adrenoceptor antagonist butoxamine or the dopamine antagonist haloperidol. This antagonism was competitive as the dose-response curve of 8-OH-DPAT was shifted to the right. Pindolol, spiperone, spiroxatrine and NAN-190 all have a high affinity for the 5-HT1A receptor. This indicates that blockade of 8-OH-DPAT-induced LLR is only possible by selective blockade of 5-HT1A receptors. A possible mechanism of action is discussed. The increased defecation induced by 8-OH-DPAT could be antagonised by pindolol and NAN-190. The effect of spiroxatrine and haloperidol on the 8-OH-DPAT-induced increase in defecation was bimodal: an increase after a low and a decrease after a high dose of 8-OH-DPAT. Metoprolol and butoxamine had no effect on the 8-OH-DPAT-induced increase in defecation, thereby excluding an influence of beta-adrenoceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

The effect of antidepressants on aversive periaqueductal gray stimulation in rats.

The selective serotonin (5-HT) uptake inhibitors fluvoxamine and sertraline had anti-aversive effects when administered acutely. Imipramine and clomipramine, which combine noradrenaline (NA) and 5-HT uptake blocking properties, did not have significant effects, whereas the mixed dopamine (DA)/NA uptake blocker nomifensine decreased the thresholds for escape from aversive periaqueductal gray stimulation. These results suggest that indirect 5-HT receptor activation suppresses periaqueductal gray aversion. Conversely, indirect DA and perhaps NA receptor activation appears to enhance periaqueductal gray aversion in rats.

1-Naphthylamine↗
PubMed1990

5-HT1C receptors in the serotonergic control of periaqueductal gray induced aversion in rats.

The functional role of brain 5-HT and 5-HT receptor subtypes in periaqueductal gray (PAG) induced aversion has been investigated in rats. Antiaversive effects were found with the serotonin agonists TFMPP, mCPP and DOI but not with RU 24969 which was found to facilitate PAG aversion. The first three serotonin agonists share potent 5-HT1C activity while RU 24969 differs with a high 5-HT1A activity. Proaversive effects were found with the mixed 5-HT1C/5-HT2 antagonists cyproheptadine and ritanserin; this effect was already reported for the mixed 5-HT1C/5-HT2 antagonists metergoline and mianserin and is opposite to the effects of the selective 5-HT2 antagonists ketanserin, pirenperone, trazodone and spiperone. The antiaversive effects of mCPP (1 mg/kg) could be prevented by pretreatment of the animals with mianserin (1 and 10 mg/kg). These results suggest that 5-HT1C receptors play an important role in the serotonergic control of PAG aversion. 5-HT1C receptor activation seems to mediate antiaversive effects whereas acute 5-HT1C receptor blockade appears to facilitate PAG aversion. Functional interactions take place between several receptor types in the in vivo control of PAG aversion, where 5-HT1C receptors appear to play a predominant function.

Amphetamines↗
PubMed1990

Involvement of 5-HT1C-receptors in drug-induced penile erections in rats.

Drug-induced penile erections (PE) were initially suggested to be 5-HT1B receptor mediated. However, since the discovery of the 5-HT1C receptor a number of compounds, considered to be 5-HT1B selective, appear to bind more strongly to the 5-HT1C receptor and this prompted a re-evaluation of the receptor subtype involved in PE induction. PE could be induced by the 5-HT agonists mCPP (0.22-2.2 mg/kg), TFMPP (0.46-1.0 mg/kg) and MK 212 (0.1-1.0 mg/kg). The 5-HT agonist DOI (0.022-0.22 mg/kg) did not induce PE in placebo-pretreated rats but in rats pretreated with various 5-HT2 antagonists it did. These compounds have in common a strong affinity for the 5-HT1C receptor, mCPP (0.46 mg/kg)-induced PE could be antagonized by the 5-HT antagonists metergoline, cyproheptadine, mesulergine, mianserin, ritanserin and ketanserin. Their ED50S were 0.04, 0.4, 0.03, 0.06, 0.4 and 2 mg/kg, respectively. The potency of both the agonists to induce, and the antagonists to inhibit, PE was found to be dependent on their selectivity for the 5-HT1C receptor versus the 5-HT2 receptor. Spiperone (0.1-1.0 mg/kg) and GR 38032F (1-10 mg/kg) did not antagonise mCPP-induced PE. 8-OH-DPAT and 5MeODMT counteracted mCPP (0.46 mg/kg)-induced PE. Their ED50S were 0.03 and 0.4 mg/kg, respectively. DOI counteracted mCPP induced PE only at doses above 1 mg/kg, whereas CGS 12066B (1.0-10 mg/kg) was inactive. The results suggest that PE are induced by activation of the 5-HT1C receptor and are functionally inhibited by activation of 5-HT1A or 5-HT2 receptors.

Animals↗
PubMed1990

Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice.

1. Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5-HT receptor subtypes was studied. 2. Hypothermia and hypoactivity in mice induced by the 5-HT1A-agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) could be attenuated by the preferential 5-HT1C-agonists MK 212, 1-(meta-chlorophenyl)-piperazine (mCPP) and m-trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5-HT2/1C-agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The mixed 5-HT1A/1B-agonist CGS 12066B at 10 mg kg-1 potentiated hypothermia and had no effect on hypoactivity. 3. Forepaw treading in rats induced by the 5-HT1A-agonist 8-OH-DPAT was attenuated by the 5-HT1C-agonists MK 212 and mCPP. The 5-HT1C-agonist TFMPP had a bimodal effect: at low doses (less than 1 mg kg-1) it potentiated, and at higher doses (greater than 2.2 mg kg-1) it attenuated forepaw treading, the mixed 5-HT2/1C-agonist DOI produced 5-HT2-related behaviours and potentiated 8-OH-DPAT-induced forepaw treading. This indicates an attenuating effect of 5-HT1C-receptor activation and a potentiating effect of 5-HT2-receptor activation. CGS 12066B had no effect in this respect. 4. Head shakes in rats induced by DOI could be attenuated by 8-OH-DPAT, TFMPP, mCPP and MK 212. The ID50S were 0.03, 0.7, 0.1 and .2 mg kg-1, respectively. This suggests that a 5-HT2-receptor-mediated effect may be attenuated by activation of 5-HT1A- or 5-HT1c-receptors. CGS 12066B attenuated the head shake response but only at 10mg kg- '. 5. The results suggest that interactions exist between the different 5-HT receptor subtype-mediated events. Therefore, care is needed in drawing conclusions from functional measurements when compounds have more or less equal affinities for more than one 5-HT-receptor subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Behavioural pharmacology of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro- 1H-dibenz[2,3:6,7]oxepino-[4,5-c]pyrrolidine maleate, a compound interacting with dopaminergic and serotonergic receptors.

trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepinol[4,5-c]pyrrolidine maleate (Org 5222) is a new compound with effects on animal behaviour indicating strong antipsychotic potential based on antagonism of dopaminergic and serotonergic effects. The compound inhibits apomorphine-induced climbing behaviour, mouse locomotor activity, rat activity in an open field, shuttle box behaviour in rats, pergolide induced circling in 6-hydroxydopamine(6-OHDA) lesioned rats, serotonin agonist-induced forepaw treading, head shakes and penile erections. The compound is less effective in inducing catalepsy, and antagonising SKF-38393 (tetrahydro- 1-phenyl-1H-3-benzazepine-7,8-diol HCl)-induced circling in 6-OHDA-lesioned rats and it does not induce perioral movements in rats. Based on these data and the neurochemical profile of the compound it was decided that this compound merits clinical investigation in a programme aiming for an effective antipsychotic agent with reduced risks of extrapyramidal side-effects.

Animals↗
PubMed1989

Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion.

8-OH-DPAT, a selective 5-HT1A agonist, and mCPP, which has preferential affinity for 5-HT1B and 5-HT1C receptors, were studied for their effects on aversive brain stimulation in rats. Opposite effects were found with these two agonists: D, L-8-hydroxy-N,N-dipropyl-2-aminotetralin HBr (8-OH-DPAT; 0.1-1.0 mg/kg i.p.) dose dependently decreased the threshold for neurostimulation-induced escape behaviour while mCPP (0.1-1.0 mg/kg i.p.) dose dependently increased the threshold. The proaversive effect of 8-OH-DPAT and the antiaversive effect of mCPP suggest that 5-HT1A and non-5-HT1a (5-HT1B or 5-HT1C) receptors play distinct roles in mechanisms of aversion, perhaps at different locations in the CNS.

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

Effects of serotonin receptor antagonists on PAG stimulation induced aversion: different contributions of 5HT1, 5HT2 and 5HT3 receptors.

The effects of serotonin receptor antagonists with differential selectivity for the various classes of 5HT receptors (5HT1, 5HT2 and 5HT3) were tested for their effects on the response to aversive brain stimulation. Electrical stimulation was administered to the dorsal part of the periaqueductal gray matter (PAG), one of the main cerebral structures subserving negative reinforcement. Stimulation frequency thresholds for escape responses were recorded before and following administration of the compounds. Ketanserin (0.32-32 mg/kg IP), trazodone (1.0-22 mg/kg), pirenperone (0.032-1.0 mg/kg) and spiperone (0.1-0.2 mg/kg) dose-dependently increased stimulation frequency thresholds necessary to induce escape responses. Opposite effects were observed with mianserin (0.01-32 mg/kg) and metergoline (0.032-10 mg/kg) which decreased threshold for escape. ICS 205-930 (0.01-10 mg/kg), did not affect the stimulation frequency threshold for escape. Prazosin (0.1-22 mg/kg) did not specifically affect aversive brain stimulation. Haloperidol (0.02-1.0 mg/kg) increased the frequency threshold for escape responses but with some motoric side effects. These data show that the various types of 5HT receptors differentially contribute to the control of central aversive systems in rats. It is suggested that blockade of 5HT2 receptors suppresses the central aversive system, whereas blockade of some 5HT1 receptors enhances aversion and overcomes the 5HT2-mediated suppression. Blockade of 5HT3 receptors has no effects. Dopamine receptor blockade further contributes to the suppression of the central aversive system. The relevance of these findings to some pathophysiological mechanisms of anxiety and depressive disorders is discussed.

Animals↗
PubMed1989

Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics.

The effects of hemicholinium-3 (HC-3) on spatial discrimination learning were studied. Rats were equipped with indwelling cannulae in the right lateral ventricle and, following recovery, were trained on a two platform spatial discrimination task in a water maze. In this task a visible escape platform remains in a fixed position in the pool during a single training session, whilst the location of an identical "float" (which affords no escape) is randomly varied. For each session the location of the fixed escape platform was changed and the rats were retrained to criterion following pretreatment either with artificial cerebrospinal fluid (CSF) or HC-3 (2.5, 5.0 micrograms/rat/ICV) 1 h before training. Each rat received every treatment according to a latin square design. The results showed that spatial learning was dose dependently impaired by HC-3, choice accuracy being reduced to chance levels by the higher dose. There was no evidence of motoric difficulty, as choice latencies were not significantly increased. Experiments were then conducted to test for reversal of the deficit using a range of psychotropic drugs. Rats were treated with CSF or HC-3 (5 micrograms/rat ICV) 60 min prior to testing and test drugs were injected 15 min before testing. Some doses of physostigmine (46-460 micrograms/kg/SC) and tetrahydroaminoacridine (THA) (2.2-10 mg/kg/SC) reversed the spatial learning deficit. The muscarinic agonists arecoline (0.046-1 mg/kg/SC), aceclidine (1-10 mg/kg/SC), oxotremorine (30-100 micrograms/kg/SC) and RS-86 (0.46, 1.0 microgram/kg/SC) were also effective. Pilocarpine (0.22-2.2 mg/kg/SC) showed marginal activity and isoarecoline (4.6-10 mg/kg/SC) was inactive. Nicotine (0.32, 1, 3.2 mg/kg/SC) and piracetam (10, 30, 100 mg/kg IP) were also inactive. The alpha 2 agonist, clonidine (46, 100 micrograms/kg SC) and the antagonist idazoxan (32, 100 micrograms/kg SC) were also inactive. Learning deficits were not reversed by haloperidol (20, 60 micrograms/kg), amphetamine (0.1, 0.46 mg/kg), the selective 5-HT1A agonist 8-OH-DPAT (30, 100 micrograms/kg) or by the benzodiazapine antagonist ZK-93426 (1, 3.2, 10 mg/kg). The results show that forebrain Ach depletion by HC-3 impairs spatial discrimination learning and these deficits are reversed by cholinesterase inhibitors and some muscarinic receptor agonists. Some degree of pharmacological selectivity is indicated by the failure of a range of other drugs to reverse the impairments.

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

Selective activation of 5HT1A receptors induces lower lip retraction in the rat.

The induction of lower lip retraction (LLR) by serotonergic (5HT) compounds and antagonism of LLR by compounds acting via a variety of receptor systems was investigated. LLR could be induced by subcutaneous injection of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), buspirone, ipsapirone or RU 24969. Inactive were the putative 5HT1B,1C agonist 1-(3'chlorophenyl)-piperazine (mCCP), the 5HT2,1C agonist (dl)-1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5HT reuptake inhibitors citalopram and paroxetine and the 5HT-releasing compounds parachloroamphetamine (PCA) and fenfluramine. 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) induced lower lip retraction after pretreatment with metergoline, cyproheptadine or ritanserin but not by itself. 8-OH-DPAT-induced LLR could be antagonised by the direct and indirect 5HT agonists mCPP, DOI, 5-MeODMT, PCA, fenfluramine and high doses of paroxetine, but not by the 5HT antagonists metergoline, methysergide, mesulergine, GR38032F, xylamidine or pirenperone. The dopamine agonists apomorphine and pergolide antagonised 8-OH-DPAT-induced LLR, whereas SKF 38393 was weakly active. No significant antagonism was found with the dopamine antagonists haloperidol and spiperone, the alpha 2 agonist clonidine and the alpha 1 antagonist prazosin and the alpha 2 antagonist idazoxan. Also inactive were the antihistaminic mepyramine, the anticholinergic atropine, the opiate antagonist naloxone and the anxiolytic chlordiazepoxide. The results suggest that, in vivo, functional interactions take place between the various 5HT receptors. The hypothesis that lower lip retraction is induced by compounds directly and selectively stimulating 5HT1A receptors is discussed.

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

Animal models for anxiety and response to serotonergic drugs.

In examining anxiety and the response of animal models to serotonergic drugs, four aspects should be taken into account: (1) the serotonin receptor is subdivided into at least six receptor subtypes; (2) benzodiazepines have acute anxiety-relieving effects, whereas antidepressants, serotonin-uptake inhibitors, buspirone, and serotonin antagonists have antianxiety effects only after prolonged administration; (3) diagnostic criteria differentiate several distinguishable anxiety disorders that have different responsiveness to serotonin-related drugs, and (4) various types of animal models exist, each responding differently to serotonin-related drugs. Perhaps particular animal models are relevant only for the study of one particular type of anxiety disorder. This differentiated view will be used when discussing the role of 5-hydroxytryptamine (5-HT) receptor subtypes in anxiety disorders and anxiety models. The 5-HT1A receptor is implicated in anxiety by the compounds buspirone and 8-hydroxy-2-(di-n-propyl-aminotetraline) (OHDPAT). The 5-HT1B or the 5-HT1D receptors play a role in the 'defensive burying' anxiety model and probably mediate antidepressant and antianxiety effects of serotonin-uptake inhibitors. The 5-HT1C receptor plays a role in the aversive brain stimulation anxiety model and could play a role in antianxiety effects of mianserin. The 5-HT2 receptor is selectively blocked by ritanserin. In animal 'conflict models' for anxiety, 5-HT-2-receptor antagonists are active, although they are weaker than the benzodiazepines. The 5-HT3-receptor antagonists are reported to be active in social interaction models for anxiety; however, clinical experience in anxiety using these compounds is not yet available.

Animals↗
PubMed1988

Apomorphine-induced limb flicks in cats: the role of dopamine receptors located outside the blood-brain barrier.

Apomorphine-induced limb flicks in cats have been ascribed to a central dopamino-mimetic action of the drug. In these experiments we investigated the role of receptors located outside the blood-brain barrier (BBB) in the induction of limb flicking. Domperidone, a dopamine-receptor blocker which does not readily pass through the BBB, antagonised the induction of limb-flicks induced by apomorphine. This suggests that limb flicking behaviour may involve interactions with receptors located before the BBB. In contrast, 6-amino-5,6,7,8-tetrahydro-1,2-naphtalenediol HBr (6-ATN), a dopamine-agonist which does not penetrate the BBB, did not induce limb flicks, indicating that receptor stimulation outside the BBB alone is not sufficient to induce limb flicks. We suggest that limb flicks in cats is a behaviour which can be elicited by combined activation of centrally located dopamine receptors and dopamine receptors in the area postrema.

Animals↗