NADPH‐diaphorase activity in the frontal cortex of NBM‐lesioned rats treated with verapamil

Caballero-Bleda, Marı́a; Redondo‐Aniorte, Francisco Javier; Aldeguer‐Montiel, Antonio; Popović, Natalija; Popovic, Marko; Puelles, Luis

doi:10.1002/nrc.1011

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…Neither acute nor chronic verapamil treatment improved foot-shock induced aggression in NBM-lesioned rats (Popovićet al, 1997c;Popovićet al, 1998b, respectively). Moreover, morphological studies indicated that long-term verapamil treatment (2.5, 5, and 10 mg/kg/12 h) produced a significant neuroprotection on NADPH-diaphorase and ChATimmunopositive cortical neurons in NBM lesioned rats (Caballero-Bleda et al, 2001;Popovićet al, 2006). The above-mentioned studies indicated that verapamil expresses an inverted U-shape mode of action (Tables 1 and 2).…”

Section: In Vivo Studiesmentioning

confidence: 87%

Verapamil and Alzheimer’s Disease: Past, Present, and Future

et al. 2020

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Verapamil is a phenylalkylamine class calcium channel blocker that for half a century has been used for the treatment of cardiovascular diseases. Nowadays, verapamil is also considered as a drug option for the treatment of several neurological and psychiatric disorders, such as cluster headache, bipolar disorders, epilepsy, and neurodegenerative diseases. Here, we review insights into the potential preventive and therapeutic role of verapamil on Alzheimer's disease (AD) based on limited experimental and clinical data. Pharmacological studies have shown that verapamil has a wide therapeutic spectrum, including antihypertensive, anti-inflammatory, and antioxidative effects, regulation of the blood-brain barrier function, due to its effect on P-glycoprotein, as well as adjustment of cellular calcium homeostasis, which may result in the delay of AD onset or ameliorate the symptoms of patients. However, the majority of the AD individuals are on polypharmacotherapy, and the interactions between verapamil and other drugs need to be considered. Therefore, for an appropriate and successful AD treatment, a personalized approach is more than necessary. A well-known narrow pharmacological window of verapamil efficacy may hinder this approach. It is therefore important to note that the verapamil efficacy may be conditioned by different factors. The onset, grade, and brain distribution of AD pathological hallmarks, the time-sequential appearances of AD-related cognitive and behavioral dysfunction, the chronobiologic and gender impact on calcium homeostasis and AD pathogenesis may somehow be influencing that success. In the future, such insights will be crucial for testing the validity of verapamil treatment on animal models of AD and clinical approaches.

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Section: In Vivo Studiesmentioning

confidence: 87%

Verapamil and Alzheimer’s Disease: Past, Present, and Future

et al. 2020

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“…The relationship between calcium homeostasis, cholinergic system activation and learning and memory, remains to be completely elucidated. Our previous studies indicated that acute and chronic verapamil treatment could ameliorate morphological, physiological, cognitive, and non-cognitive behavioral dysfunctions in rats with cholinergic depletion, suggesting possible relations between cholinergic function and calcium metabolism ( Popović et al, 1997a , b , c , 1998a , b , 1999 , 2006 ; Caballero-Bleda et al, 2001 ). Similarly, Sekhar et al (2016) demonstrated that verapamil improves scopolamine-induced memory impairment in elevated plus maze and novel object recognition tests.…”

Section: Introductionmentioning

confidence: 99%

Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats

et al. 2017

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Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0.5, 1.0, 2.5, 5.0, 10, or 20 mg/kg i.p.) as well as the interaction between scopolamine and verapamil on memory consolidation in the step-through passive avoidance task, in Wistar rats. Our results showed that verapamil (1.0 and 2.5 mg/kg) administered immediately after the acquisition task significantly increased the latency of the passive avoidance response, on the 48 h retested trial, improving memory consolidation. On the other hand, verapamil in a dose of 5 mg/kg, that per se does not affect memory consolidation, significantly reversed the memory consolidation improvement induced by scopolamine (1 mg/kg, i.p., administered immediately after verapamil treatment) but did not change the passive avoidance response in rats treated by an ineffective dose of scopolamine (30 mg/kg). In conclusion, the present data suggest that (1) the post-training administration of verapamil, dose-dependently, improves the passive avoidance response; (2) verapamil, in ineffective dose, abolished the improvement of memory consolidation effect of scopolamine; and (3) exists interaction between cholinergic muscarinic receptors and calcium homeostasis-related mechanisms in the consolidation of emotional memory.

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Verapamil prevents, in a dose-dependent way, the loss of ChAT-immunoreactive neurons in the cerebral cortex following lesions of the rat nucleus basalis magnocellularis

et al. 2005

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In the present study we analysed the neuroprotective effect of the L-type voltage-dependent calcium channel antagonist verapamil on cholineacetyltransferase (ChAT)-immunoreactive neurons in the cerebral cortex of rats with bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM). Treatment with verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg/12 h i.p.) started 24 h after NBM lesions and lasted 8 days. Animals were sacrificed on day 21 after NBM-lesions. The bilateral NBM-lesions produced significant loss of ChAT-immunoreactive neurons in frontal, parietal and temporal cortex. Although the number of ChAT-positive neurons was significantly higher in NBM-lesioned animals treated with verapamil at a dose of 2.5, 5.0 and 10.0 mg/kg than in saline treated ones, the most significant effect was obtained at a dose of 5 mg/kg. This is, to our knowledge, the first report showing an inverted U-shape mode of neuroprotective action of the calcium antagonist verapamil, at morphological level in this particular model of brain damage. The demonstrated beneficial effect of verapamil treatment suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a possible treatment to prevent neurodegenerative processes in the rat cerebral cortex.

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NADPH‐diaphorase activity in the frontal cortex of NBM‐lesioned rats treated with verapamil

Cited by 4 publications

References 23 publications

Verapamil and Alzheimer’s Disease: Past, Present, and Future

Verapamil and Alzheimer’s Disease: Past, Present, and Future

Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats

Verapamil prevents, in a dose-dependent way, the loss of ChAT-immunoreactive neurons in the cerebral cortex following lesions of the rat nucleus basalis magnocellularis

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