Effects on ingestive behavior in rats of the α1-adrenoceptor agonist cirazoline

doi:10.1016/0014-2999(92)90645-K

European Journal of Pharmacology

Volume 210, Issue 1, 7 January 1992, Pages 11-16

https://doi.org/10.1016/0014-2999(92)90645-K Get rights and content

Abstract

Microinjections of various α₁-adrenoceptor agonists including phenylephrine and phenylpropanolamine into the paraventricular hypothalamic nucleus (PVN) suppress food intake in rats, suggesting that this receptor type might act in opposition to previously identified facilatory PVN α₂-adrenoceptors in the modulation of feeding. In the present experiments, we examine the effects on food and water intake of intra-PVN as well as systemic injection of cirazoline, a highly potent α₁-adrenoceptor agonist. In Experiment 1, intra-PVN microinjection of cirazoline (0, 3, 6, 12 and 24 nmol) suppressed food intake (ED₅₀ = 23.4 nmol) without significant effects on water intake. In Experiment 2, systemic injection of cirazoline (0, 0.05, 0.1, 0.2, 0.4 mg/kg) also markedly suppressed food intake (ED₅₀ = 0.05 mg/kg i.p.), with a less potent action on water intake (ED₅₀ = 0.22 mg/kg i.p.). The results of this study as well as our previous investigations strongly support the notion that α₁-adrenoceptors within rat PVN act to reliably suppress food intake.

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The alpha-1 adrenergic agonist, cirazoline, was examined for effects on spatial working memory performance in aged rhesus monkeys. Cirazoline has additional high affinity for imidazoline receptors and has good brain penetrance when administered systemically. Spatial working memory was assessed using the variable delayed response task, a test dependent upon prefrontal cortical function in monkeys. Low doses of cirazoline (0.00001–0.001 mg/kg) impaired delayed response performance significantly. This impairment did not appear to result from nonspecific changes in behavior, because cirazoline had no significant effect on performance of control trials where the delay was “0” s, and had no significant effect on behavioral ratings. Impairment was reversed by pretreatment with the alpha-1 adrenergic antagonist, prazosin, consistent with drug actions at alpha-1 adrenergic receptors. In contrast, preliminary data suggest that higher cirazoline doses (0.001–0.01 mg/kg) occasionally produced improved performance that was not reversed by prazosin, but rather, by the imidazoline/alpha-2 adrenergic antagonist, idazoxan. The finding that alpha-1 adrenergic receptor stimulation impairs spatial working memory performance complements previous research demonstrating that alpha-2 adrenergic receptor stimulation improves working memory, and suggests that norepinephrine may have opposing actions at alpha-1 vs. alpha-2 receptors in the prefrontal cortex as it does in the hypothalamus and thalamus.

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Effects on ingestive behavior in rats of the α1-adrenoceptor agonist cirazoline

Abstract

Trends Pharmacol. Sci.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Brain Res. Bull.

Life Sci.

Physiol. Beh.

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Brain Res.

Psychoneuroendocrinology

Brain Res.

Neurosci. Biobehav. Rev.

Pharmacol. Biochem. Beh.

Brain Res. Bull.

Pharm. Biochem. Behav.

Functional and biochemical evidence for the lack of cardiac presynaptic alpha-adrenoceptor agonist properties of cirazoline (LD 3098)

Br. J. Pharmacol.

Applied Statistics and the SAS Programming Language

Norephedrine (phenylpropanolamine) stimulates oxygen consumption and lactate production in the perfused rat hindlimb

Int. J. Obesity

Effects on ingestive behavior in rats of the α₁-adrenoceptor agonist cirazoline