Receptor Agonists In Mice Research Articles

Different function of spinal 5-HT 1A and 5-HT 2 receptor subtypes in modulating behaviour induced by excitatory amino acid receptor agonists in mice

The modulating effects of 5-HT 1A and 5-HT 2 receptor agonists on behaviour induced by spinal excitatory amino acid (EAA) agonists were examined. Intrathecal (i.th.) administration of both N-methyl- d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) produce a behavioural syndrome of caudally directed biting and scratching. Serotonin (5-HT) agonists were coadministered with either NMDA or AMPA, and changes in EAA-induced behaviour were scored. All drugs were administered i.th. The 5-HT 1A agonist8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (15–60 nmol) reduced both NMDA (0.25 nmol) and AMPA (0.06 nmol) induced behaviour in a dose-dependent manner, and preadministration of the 5-HT 1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)bytyl]piperazine hydrobromide (NAN-190) (20 nmol) reversed this effect. The administration of the 5-HT agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.7–28 nmol) produced a dose-dependent behavioural syndrome similar to the EAA agonists. This was reversed by preadministration of ritanserin (10 nmol), a 5-HT 2 antagonist. When DOI was coadministered with NMDA (0.25 nmol) or AMPA (0.06 nmol) there was an increase in the behaviour recorded and this effect was antagonised by ritanserin. The results of this study implicate that in the spinal cord subtypes of 5-HT receptors have different effects on modulation of behaviour induced by activation of the NMDA or the MPA receptors; the activated 5-HT 1A receptors have an inibibitory effect whereas activation of the 5-HT 2 receptors enhance the induced behaviour.

Differential modulation of μ-opioid receptor-mediated antitussive activity by δ-opioid receptor agonists in mice

We examined the effect of [D-Ala 2]deltorphin II, a selective δ 2-opioid receptor agonist, on the antitussive effect of [D-Ala 2, MePhe 4, Gly-ol 5]enkephalin (DAMGO), a selective μ-opioid receptor agonist. [D-Ala 2]deltorphin (3 nmol i.c.v.) had no significant effect on the number of coughs. However, upon i.c.v. pretreatment with [D-Ala 2]deltorphin II (3 nmol) the antitussive activity of DAMGO (0.03 nmol) was significantly enhanced. The enhancement of the antitussive activity of DAMGO caused by [D-Ala 2]deltorphin II was prevented by a benzofuran derivative of naltrindole (0.1 mg/kg s.c.), a selective δ 2-opioid receptor antagonist. These results suggest that δ 2-opioid receptors may play a synergistic role in antitussive processes that are mediated by μ-opioid receptors.

Partial and full dopamine D 1 receptor agonists in mice and rats: relation between behavioural effects and stimulation of adenylate cyclase activity in vitro

The dopamine (DA) D 1 agonists, SK&F 83959, SK&F 75670, SK&F 38993, SK&F 81297 and SK&F 80723, had variable abilities to stimulate adenylate cyclase activity in rat striatal homogenates. Their efficacies, in relation to the effect of 100 μM DA were 0, 33, 69, 68 and 81%, respectively. In rats, all compounds induced (1) contralateral circling behaviour after unilateral 6-hydroxy-DA lesions, (2) ipsilateral circling behaviour after midbrain hemitransection after cotreatment with the D 2 agonist quinpirole and (3) oral stereotypies after their combination with quinpirole. Maximum effects and rank order of potencies were similar in the three test models. In mice SK&F 83959, SK&F 75670 and SK&F 38393 inhibited methylphenidate-induced gnawing behaviour and induced no or only weak hypermotility. SK&F 81297 induced marked hypermotility which was partially inhibited by SK&F 83959 and SK&F 75670 and was completely blocked by the D 1 antagonist, SCH 23390. It is concluded that no relation could be demonstrated between the efficacy to stimulate adenylate cyclase and to induce circling behaviours and stereotypies in rats. In contrast, a relation between biochemical and behavioural efficacies was found in the mouse models. The results suggest that different subtypes of D 1 receptors mediate the behavioural effects reported in this study.

P-Chlorophenylalanine attenuates the pituitary-adrenocorticol response to 5-HT 1A receptor agonists in mice

The i.p. injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) caused hypothermia and increased the concentrations of serum corticosterone and plasma ACTH in mice. The effects of 8-OH-DPAT at a dose of 2 mg/kg but not of 0.2 mg/kg on the hormone levels were attenuated by pretreatment with p-chlorophenylalanine (pCPA) which depleted brain 5-HT by about 70%; the hypothermic effect of 8-OH-DPAT was, however, not prevented. Similar results were obtained with another 5-HT 1A agonist, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554).

P-012 - Hyperthermic effects of a 5-HT-2 receptor agonist in mice

P-012 - Hyperthermic effects of a 5-HT-2 receptor agonist in mice

Behavioural effects of 5-HT-1A receptor agonists in mice

Behavioural effects of 5-HT-1A receptor agonists in mice

Chronic treatment with the potential antidepressant drug rolipram: the effect on the behavioural responses to adrenergic and dopaminergic receptor agonists with some biochemical correlates.

We studied the effect of acute and chronic treatment with rolipram, a potential antidepressant drug, on the behavioural responses induced by adrenergic and dopaminergic receptor agonists in mice and rats, and on (3H)prazosin and (3H)dihydroalprenolol binding to cortical membranes and whole brain noradrenaline and dopamine utilization in rats. Chronic, but not acute, administration of rolipram potentiated a behavioural response mediated through central alpha 1-adrenoceptors, attenuated an alpha 2-adrenoceptor-mediated response and inhibited a beta-adrenoceptor-mediated response. Neither treatment affected the behavioural responses to dopaminergic stimulants. Repeated treatment with rolipram decreased the density of cortical (3H)dihydroalprenolol, but not (3H)prazosin bindings sites, and reduced brain noradrenaline, but not dopamine utilization. These results suggest that chronic administration of rolipram induces the down-regulation of the central beta- and alpha 2-adrenoceptors and enhances the responsiveness of the central alpha 1-adrenoceptors with no apparent changes in the alpha 1-adrenoceptor density.

Bromocriptine potentiates the behavioural effects of directly and indirectly acting dopamine receptor agonists in mice.

After an initial period of depression which lasted up to 90 min following injection, bromocriptine (BRC, 5-20 mg/kg, IP) produced dose-dependent and long lasting (7 h) locomotor stimulation in mice. The locomotor stimulation was antagonised by reserpine, alpha-methyl-p-tyrosine (AMPT) or haloperidol. The blockade by AMPT of BRC's locomotor stimulant effect was reversed by prior treatment of the mice with a low, behaviourally inactive dose of L-Dopa plus benserazide. In mice pretreated with reserpine, BRC enhanced the stimulant action of d-amphetamine. Moreover, in mice pretreated with reserpine plus AMPT, BRC significantly enhanced the locomotor stimulant effect of apomorphine. This ability of BRC to enhance the effect of apomorphine commenced as soon as 20 min after BRC administration and lasted for at least 8 h. The dopamine (DA) uptake inhibitor and DA receptor agonist nomifensine potentiated and prolonged the stimulant effect of BRC while inhibitors of the neuronal uptake of noradrenaline (desipramine) and 5-hydroxytryptamine (fluoxetine) were without marked effect. The results clearly show that BRC, in behavioural terms, has no efficacy per se at the postsynaptic DA receptor and that it requires either DA or the administration of an exogenous agonist such as apomorphine for the expression of its effects.