Blockade Of Α2-adrenergic Receptors Research Articles

Blockade of α2-adrenergic receptors in prelimbic cortex: impact on cocaine self-administration in adult spontaneously hypertensive rats following adolescent atomoxetine treatment.

Research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder demonstrated that chronic methylphenidate treatment during adolescence increased cocaine self-administration established during adulthood under a progressive ratio (PR) schedule. Compared to vehicle, chronic atomoxetine treatment during adolescence failed to increase cocaine self-administration under a PR schedule in adult SHR. We determined if enhanced noradrenergic transmission at α2-adrenergic receptors within prefrontal cortex contributes to this neutral effect of adolescent atomoxetine treatment in adult SHR. Following treatment from postnatal days 28-55 with atomoxetine (0.3mg/kg) or vehicle, adult male SHR and control rats from Wistar-Kyoto (WKY) and Wistar (WIS) strains were trained to self-administer 0.3mg/kg cocaine. Self-administration performance was evaluated under a PR schedule of cocaine delivery following infusion of the α2-adrenergic receptor antagonist idazoxan (0 and 10-56μg/side) directly into prelimbic cortex. Adult SHR attained higher PR break points and had greater numbers of active lever responses and infusions than WKY and WIS. Idazoxan dose-dependently increased PR break points and active lever responses in SHR following adolescent atomoxetine vs. vehicle treatment. Behavioral changes were negligible after idazoxan pretreatment in SHR following adolescent vehicle or in WKY and WIS following adolescent atomoxetine or vehicle. α2-Adrenergic receptor blockade in prelimbic cortex of SHR masked the expected neutral effect of adolescent atomoxetine on adult cocaine self-administration behavior. Moreover, greater efficacy of acute idazoxan challenge in adult SHR after adolescent atomoxetine relative to vehicle is consistent with the idea that chronic atomoxetine may downregulate presynaptic α2A-adrenergic autoreceptors in SHR.

Hemodynamic responses to electrical stimulation of the aortic depressor nerve, in conscious rats, after α2 adrenergic receptor blockade

We evaluated the attendant of postjunctional α2 adrenergic receptors in the hemodynamic response to electrical stimulation of the aortic depressor nerve (ADN) in conscious rats. The efficacy of MK‐467, a selective α2 adrenergic receptor antagonist, in attenuating the hypertensive and bradycardic response to clonidine, an α2 adrenergic receptor agonist, was also evaluated. The animals were anesthetized (sodium pentobarbital) for catheterization of femoral artery and vein, and placement of electrodes for ADN stimulation. Three sets of electrical stimulation (20s, 1mA, 2ms and 60 Hz) was applied before and after (10, 20 and 30 min) the administration of MK‐467 (3mg/kg iv). ADN stimulation (n=7) elicited a hypotensive response which was not affected by MK‐467 (−36±4, −41±2, −32±4 vs −37±3, −32±5, −31±5 mmHg before). Nevertheless, the bradycardic response after MK‐467 was enhanced (−123±25, −85±16, −60±14 vs −46±8, −41±7, −45±8 bpm before). MK‐467 (n=7) remarkably attenuated the hypertensive (5±4 vs 40±3 mmHg before) and the bradycardic (−10±5 vs −58±9 bpm before) response to clonidine (1.5 mg/kg iv). The results demonstrate that MK‐467 promoted a remarkable blockade of the peripheral α2 adrenergic receptor, but did not affect the hypotensive response produced by electrical ADN stimulation, precluding a role played by the deactivation of postjunctional α2 adrenergic receptors in this hypotensive response.

Paliperidone as an Alternative for Risperidone in a Case of Schizophrenia With Retrograde Ejaculation

Paliperidone as an Alternative for Risperidone in a Case of Schizophrenia With Retrograde Ejaculation

Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine: Involvement of α2 adrenergic receptors

Having previously observed that noradrenaline activation of β adrenergic receptors induces the synthesis of the chemokine monocyte chemoattractant protein (CCL2/MCP-1) in astrocytes, it is our interest to analyze the mechanisms involved in this process, particularly the possible effect of noradrenaline-modulating drugs. The treatment of primary rat astrocyte cultures with the noradrenaline transporter inhibitors desipramine or atomoxetine induced the expression and synthesis of CCL2/MCP-1 in these cells. This effect of both drugs in vitro suggests that CCL2/MCP-1 expression could also be modulated by some mechanism independent of the elevation of brain noradrenaline levels. This was confirmed by measuring a reduction in CCL2/MCP-1 production by the treatment with the α2 adrenergic receptor agonist clonidine. Accordingly, the blockade of α2 adrenergic receptors with yohimbine potentiated the production of MCP-1 stimulated by the activation of β receptors. While the activation of β adrenergic receptors and the subsequent elevation of cAMP levels seem to be the main pathway for noradrenaline to induce CCL2/MCP-1 in astrocytes, our data indicate that the α2 adrenergic receptors also regulate CCL2/MCP-1 expression working as inhibitory mediators.

Atypical antipsychotics: matching receptor profile to individual patient's clinical profile.

Understanding common pharmacologic and clinical "class" actions associated with atypical antipsychotics certainly reveals how these agents are alike, but what about unique differences from one agent to another? Atypical antipsychotics are also a heterogeneous group of agents that have complex pharmacologic entities, acting upon multiple dopamine receptors (D2, D1, D3, and D4) and multiple serotonin receptors (5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1D, among others). Atypical antipsychotics also interact with noradrenergic (alpha 1- and alpha 2-adrenergic receptor blockade), histaminergic (H1-receptor blockade), and cholinergic (muscarinic M1 blockade) neurotransmitter systems as well as with monoamine (D, 5-HT, and norepinephrine reuptake blockade) transporters. However, no two atypical antipsychotics possess the same portfolio of actions upon all of these additional neurotransmitter systems.

Blockade of α2-adrenergic Receptors Markedly Potentiates Glutamate-evoked Activity of Locus Coeruleus Neurons

The locus coeruleus (LC) is a small pontine nucleus with widely distributed efferents that supply the majority of norepinephrine in brain. Evidence from our laboratory has implicated α2-adrenergic receptors on LC neurons in regulating the magnitude of the bursting response of LC neurons to both sensory stimulation and systemically administered drugs. Sub-stimulation of α2-adrenergic receptors in the LC and the resulting hyper-responsiveness of LC neurons is thought to at least partially mediate depression in an animal model. The present study extends previous work in our laboratory by demonstrating that blockade of α2-adrenergic receptors also markedly augments the bursting response of LC neurons to locally – via microiontophoresis-applied glutamate.

Blockade of endotoxin-induced cecal hypoperfusion and ileus with an α2 antagonist in horses

Summary Stimulation of α2 adrenergic receptors inhibits colonic motility and may constrict some peripheral vascular beds. Endotoxemia elicits release of sympathetic neurotransmitters and increases sympathetic nerve activity, which may result in stimulation of α2 adrenergic receptors. The objective of this study was to determine whether blockade of α2 adrenergic receptors would restore cecal motility and blood flow during endotoxemia in horses. Strain-gauge force transducers and ultrasonic flow probes were used to measure cecal and colonic mechanical activity and lateral cecal arterial blood flow. Intravenous infusion of endotoxin (cumulative dose of 0.03 mg/kg) significantly decreased cecal and right ventral colon contractile activity and lateral cecal arterial blood flow. Slow iv infusion of yohimbine (cumulative dose of 75 μg/kg) significantly attenuated those effects of endotoxin. On the basis of our findings, we concluded that endotoxemia causes cecal and proximal colonic ileus and cecal hypoperfusion via a mechanism that involves α2 adrenergic receptors.

Plasma immunoreactive atrial natriuretic factor is inhibited by selective blockade of alpha 2-adrenergic receptors in conscious Sprague-Dawley rats.

Effects of alpha 2-adrenergic receptors and calcium channel blockade on basal and clonidine-stimulated immunoreactive atrial natriuretic factor (IR-ANF) in conscious Sprague-Dawley rats were evaluated. Clonidine was injected intravenously (i.v.) in a dose of 50 micrograms. Yohimbine and verapamil were used as a pretreatment, with clonidine in a dose of 50 micrograms and 0.5 mg respectively. The effects of yohimbine (1, 20, 50 micrograms) and verapamil (0.5 mg) on basal IR-ANF were also studied. Plasma IR-ANF was measured by radioimmunoassay with prior extraction on heat-activated Vycor glass. Clonidine injection in a dose of 50 micrograms caused a marked increase of plasma IR-ANF from 34.0 +/- 7.0 pg/ml (mean +/- S.E.M.) to 457.1 +/- 66.3 pg/ml. Clonidine-stimulated ANF secretion was partially inhibited by yohimbine from 457.1 +/- 66.3 pg/ml (mean +/- S.E.M.) to 99.9 +/- 23.1 pg/ml. Moreover, yohimbine in highest doses (50 micrograms) decreased the basal plasma IR-ANF from 34.0 +/- 7.0 pg/ml (means +/- S.E.M.) to 6.8 +/- 3.6 pg/ml. Verapamil did not alter basal and clonidine stimulated IR-ANF. These results indicate the important role played by alpha 2-adrenergic receptors in mediating ANF release.