Effects of Selective Activation of M1 and M4 Muscarinic Receptors on Object Recognition Memory Performance in Rats

• Published in: Pharmacology Vol. 93; no. 1-2; pp. 57 - 64
• Main Authors: Galloway, Claire R., Lebois, Evan P., Shagarabi, Shezza L., Hernandez, Norma A., Manns, Joseph R.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 2014
• Subjects: Animal memory; Animals; Benzamides - pharmacology; Biphenyl Compounds - pharmacology; Male; Memory - drug effects; Pharmacology; Pyridines - pharmacology; Rats; Rats, Long-Evans; Receptor, Muscarinic M1 - agonists; Receptor, Muscarinic M1 - physiology; Receptor, Muscarinic M4 - agonists; Receptor, Muscarinic M4 - physiology; Rodents; Short Communication; Thiophenes - pharmacology; Schizophrenia; Muscarinic receptor; Alzheimer's disease; Memory; Acetylcholine receptor
• ISSN: 0031-7012; 1423-0313; 1423-0313
• DOI: 10.1159/000357682

Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M 1 or M 4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M 1 or M 4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M 1 agonist VU0364572, the M 1 positive allosteric modulator BQCA or the M 4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M 1 and M 4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M 1 or M 4 receptors to improve memory performance in individuals with impaired memory.