The quipazine- and TFMPP-increased conditioned avoidance response in rats: role of 5HT1C/5-HT2 receptors.
Journal - Neuropharmacology (ENGLAND )
The role of serotonin (5-HT) in the acquisition of the conditioned avoidance response was investigated. The effects of different serotonin agonists and antagonists, administered prior to learning sessions, were studied in groups of naive rats using the two-way shuttle box. Quipazine, an agonist at 5-HT1B/1C/2 receptors, significantly increased avoidance responding in a dose-dependent manner (1.25-10 mg/kg, s.c.). The putative 5-HT1B/1C receptor agonist TFMPP (1-[m-trifluoromethylphenyl] piperazine) at doses of 1.25 and 2.5 mg/kg (s.c.), increased acquisition of conditioned avoidance but showed no significant difference from control at doses of 5 and 10 mg/kg. The 5-HT1A agonist, buspirone, significantly decreased acquisition of conditioned avoidance. Increased acquisition of conditioned avoidance induced by either quipazine or TFMPP was effectively antagonized by the mixed 5-HT 1C/2 receptor antagonists, ketanserin (0.2 and 2 mg/kg, s.c.) and mianserin (1 mg/kg, s.c.). In contrast, spiperone (5-HT1A/2 receptors antagonist: 0.2 mg/kg, s.c.) only inhibited the increased acquisition induced by TFMPP. On the other hand, the 5-HT1A/1B receptors antagonist, pindolol, failed to antagonize the increase in acquisition of conditioned avoidance caused by quipazine or TFMPP. These results suggest that quipazine increases the conditioned avoidance behaviour by an action that might be mediated through stimulation of 5-HT1C receptors. The acquisition of conditioned avoidance induced by TFMPP, which was blocked by ketanserin, mianserin and spiperone but not by pindolol, suggests the involvement of 5-HT1C/2 receptors in the action of TFMPP.
|ISSN : ||0028-3908|
|Mesh Heading : ||Animals Avoidance Learning Conditioning, Operant Ketanserin Male Mianserin Nadolol Pindolol Piperazines Prazosin Quipazine Rats Rats, Sprague-Dawley Receptors, Serotonin Reference Values Serotonin Agonists Serotonin Antagonists Spiperone Tropanes drug effects pharmacology pharmacology pharmacology pharmacology pharmacology drug effects pharmacology pharmacology pharmacology|
|Mesh Heading Relevant : ||drug effects pharmacology pharmacology physiology pharmacology|
Enhancement of imipramine-induced rat brain beta-adrenoreceptor desensitization by subacute co-administration of trazodone, zimelidine, quipazine or 5-hydroxytryptophan.
Journal - Psychopharmacology (GERMANY )
The present work was undertaken to characterize the role of serotonin in the regulation of beta-adrenoceptors utilizing isoprenaline-induced water drinking in the rat. For this purpose, a serotonin precursor, 5-hydroxytryptophan (24.3 mg/kg/day, PO), the serotonin neuronal uptake blockers, trazodone (18.5 mg/kg/day, PO), or zimelidine (14.6 mg/kg/day, PO) or a serotonin agonist, quipazine (12.6 mg/kg/day, PO) were administered either alone or in combination with imipramine for a period of 4 days. While none of these drugs alone showed any significant effect in attenuating the effects of isoprenaline-induced water drinking, their co- administration with imipramine did produce a significant reduction in isoprenaline-induced drinking. Simultaneous injection of the serotonin synthesis inhibitor, p-chlorophenylalanine (200 mg/kg/day, IP), has resulted in blockade of this acceleration of desensitization of beta-adrenoceptors produced by the subacute co-administration of trazodone or quipazine with imipramine. The selective 5HT2 receptor antagonist ketanserin (4 mg/kg/day/ IP) significantly inhibited the attenuation of the isoprenaline-induced drinking attained by the co-administration of quipazine with imipramine, while methysergide (2 mg/kg/day, IP) which blocks both 5HT1 and 5HT2 receptors failed to produce a significant effect on this response. These results indicate that the inhibition of the synaptosomal uptake of serotonin by quipazine seems to be more pertinent than its serotoninergic agonistic effect in the desensitization of central beta-adrenoceptors in the rat. Thus, it can be concluded that noradrenaline and serotonin are both required for the process of the desensitization of central beta-adrenoceptor systems by antidepressants.
|ISSN : ||0033-3158|
|Mesh Heading : ||5-Hydroxytryptophan Animals Brain Chemistry Drinking Behavior Female Fenclonine Imipramine Isoproterenol Ketanserin Methysergide Propranolol Quipazine Rats Rats, Inbred Strains Receptors, Adrenergic, beta Serotonin Antagonists Trazodone Zimeldine pharmacology drug effects pharmacology pharmacology pharmacology pharmacology pharmacology pharmacology pharmacology pharmacology|
|Mesh Heading Relevant : ||drug effects pharmacology drug effects pharmacology|
Interaction of some atypical antidepressants and adrenoceptor antagonists with imipramine: a behavioural study with isoprenaline-induced drinking.
Journal - Neuropharmacology (ENGLAND )
The systemic administration of isoprenaline to rats produced a dose-dependent increase in drinking which was antagonized by propranolol. While oral administration of the antidepressant, imipramine, alone had no significant effect on this response, the increase was significantly inhibited by administration of imipramine together with each of the following drugs over a period of 4 days: bupropion (21.0 mg/kg/day, p.o.), a selective inhibitor of the uptake of dopamine and nomifensine (10.6 mg/kg/day, p.o.), a relatively selective dopamine and a blocker of the uptake of noradrenaline. Similarly, the combination of the selective alpha 1-adrenoceptor antagonist, prazosin (2.37 mg/kg/day, p.o.); the selective alpha 2-adrenoceptor antagonist, yohimbine (2.38 mg/kg/day, p.o.) or the non-selective alpha-adrenoceptor blocker, phentolamine (4.65 mg/kg/day, p.o.) with imipramine caused a significant inhibition of the isoprenaline-induced drinking. It is concluded that fast desensitization of central beta-adrenoceptors in the rat can be produced after the oral subacute simultaneous administration of imipramine with alpha-adrenoceptor antagonists or atypical antidepressants, such as nomifensine or bupropion.
|ISSN : ||0028-3908|
|Mesh Heading : ||Adrenergic alpha-Antagonists Animals Antidepressive Agents Drinking Drug Interactions Female Imipramine Isoproterenol Rats Rats, Inbred Strains|
|Mesh Heading Relevant : ||pharmacology pharmacology drug effects antagonists & inhibitors pharmacology|
Desensitization of beta-adrenoceptors following repeated injections of 2-substituted 4-phenylquinolines.
Journal - The Journal of pharmacy and pharmacology (ENGLAND )
The chronic effects of five 2-substituted 4-phenylquinoline derivatives on the sensitivity of the noradrenergic cyclic AMP-generating system in the rat brain cortex have been determined, and compared with those of the typical and atypical antidepressants imipramine and trazodone, respectively. Acute treatment (single i.p. dose of 20 mg kg-1) and sub-chronic treatment (20 mg kg-1 daily for 10 days) induced no significant desensitization of the beta-adrenoceptors. However, chronic treatment (20 mg kg-1 daily for 3 weeks) significantly decreased the isoprenaline-induced increase in cyclic AMP, suggesting desensitization. This effect, coupled with previous findings, points to a potential role of these compounds as antidepressants.
|ISSN : ||0022-3573|
|Mesh Heading : ||Animals Brain Cyclic AMP Imipramine Male Quinolines Rats Rats, Inbred Strains Receptors, Adrenergic, beta Trazodone drug effects metabolism biosynthesis pharmacology pharmacology|
|Mesh Heading Relevant : ||pharmacology drug effects|