Drug Res (Stuttg) 2015; 65(2): 86-90
DOI: 10.1055/s-0034-1372646
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Rolipram and Zaprinast on Learning and Memory in the Morris Water Maze and Radial Arm Maze Tests in Naive Mice

F. Akar
1   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
O. Mutlu
1   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
I. K. Celikyurt
1   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
G. Ulak
1   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
F. Erden
1   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
E. Bektas
1   Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Turkey
,
P. Tanyeri
2   Department of Pharmacology, Faculty of Medicine, Sakarya University, Sakarya, Turkey
› Author Affiliations
Further Information

Publication History

received 07 February 2014

accepted 26 March 2014

Publication Date:
24 April 2014 (online)

Abstract

Inhibition of phosphodiesterase 5 (PDE) improved recognition memory and counteracted spatial learning impairment induced by nitric oxide synthase (NOS) inhibition in recent studies. Aim of this study was to investigate effects of rolipram, a PDE4 inhibitor and zaprinast, a PDE5 inhibitor, on learning and memory in Morris water maze (MWM) and radial arm maze (RAM) tests in naive mice. Male Balb-c mice were treated subchronically with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) for 6 days in the MWM test and acutely before the retention trial of radial arm maze test. Rolipram (0.05 and 0.1 mg/kg) significantly decreased escape latency between 2nd and 5th sessions, while zaprinast (10 mg/kg) significantly decreased escape latency only in 2nd session. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly increased time spent in escape platform’s quadrant in probe trial of MWM test; only rolipram decreased mean distance to platform, while zaprinast had no effect on mean distance to platform. Zaprinast (3 and 10 mg/kg) significantly decreased number of errors compared to control group, while rolipram (0.05 and 0.1 mg/kg) had no effect on number of errors in retention trial of RAM test. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly decreased time spent to complete retention trial (latency) compared to control group. Our study revealed that both zaprinast and rolipram enhanced spatial memory in MWM, while zaprinast seems to have more memory enhancing effects compared to rolipram in radial arm maze test.

 
  • References

  • 1 Gong B, Vitolo OV, Trinchese F et al. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. J Clin Invest 2004; 114: 1624-1634
  • 2 Vitolo OV, Sant’Angelo A, Costanzo V et al. Amyloid beta-peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proc Natl Acad Sci USA 2002; 99: 13217-13221
  • 3 Halene TB, Siegel SJ. PDE inhibitors in psychiatry – future options for dementia, depression and schizophrenia?. Drug Discov Today 2007; 12: 870-878
  • 4 Rutten K, Basile JL, Prickaerts J et al. Selective PDE inhibitors rolipram and sildenafil improve object retrieval performance in adult cynomolgus macaques. Psychopharmacology (Berl) 2008; 196: 643-648
  • 5 Prickaerts J, de Vente J, Honig W et al. cGMP, but not cAMP, in rat hippocampus is involved in early stages of object memory consolidation. Eur J Pharmacol 2002; 436: 83-87
  • 6 Son H, Lu YF, Zhuo M et al. The specific role of cGMP in hippocampal LTP. Learn Mem 1998; 5: 231-245
  • 7 Blokland A, Schreiber R, Prickaerts J. Improving memory: a role for phosphodiesterases. Curr Pharmacol Design 2006; 12: 2511-2523
  • 8 Tully T, Bourtchouladze R, Scott R et al. Targeting the CREB pathway for memory enhancers. Nat Rev Drug Discov 2003; 2: 267-277
  • 9 Zhang HT, O’Donnell JM. Effects of rolipram on scopolamine induced impairment of working and reference memory in the radial-arm maze tests in rats. Psychopharmacology 2000; 150: 311-316
  • 10 Imanishi T, Sawa A, Ichimaru Y et al. Ameliorating effects of rolipram on experimentally induced impairments of learning and memory in rodents. Eur J Pharmacol 1997; 321: 273-278
  • 11 Zhang HT, Huang Y, Suvarna NU et al. Effects of the novel PDE4 inhibitors MEM1018 and MEM1091 in models of memory and antidepressant sensitivity. Soc Neurosci Abstr 2002; 684: 12
  • 12 Prickaert J, van Staveren WC, Şık A et al. Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat. Neuroscience 2002; 113: 351-361
  • 13 Prickaerts J, Şık A, van Staveren WC et al. Phosphodiesterase type 5 inhibition improves early memory consolidation of object information. Neurochem Int 2004; 45: 915-928
  • 14 Prickaerts J, Steinbusch HWM, Smits JFM et al. Possible role of nitric oxide-cyclic GMP pathway in object recognition memory: effects of 7-nitroindazole and zaprinast. Eur J Pharmacol 1997; 337: 125-136
  • 15 Domek-Lopacinska K, Strosznajder JB. The effect of selective inhibition of cyclic GMP hydrolyzing phosphodiesterases 2 and 5 on learning and memory processes and nitric oxide synthase activity in brain during aging. Brain Res 2008; 1216: 68-77
  • 16 Beuzen A, Belzung C, Roullet P. Drug effects in a radial maze designed for dissociation of cues used by mice. Pharmacol Biochem Behav 1994; 48: 23-29
  • 17 Belzung C, Le Guisquet AM, Griebel G. b-CCT, a selective BZ-v receptor antagonist, blocks the anti-anxiety but not the amnesic action of chlordiazepoxide in mice. Behav Pharmacol 2000; 11: 125-131
  • 18 Reneerkens OA, Rutten K, Steinbusch HW et al. Selective phosphodiesterase inhibitors: a promising target for cognition enhancement. Psychopharmacology (Berl) 2009; 202: 419-443
  • 19 Menniti FS, Chappie TA, Humphrey JM et al. Phosphodiesterase 10 A inhibitors: a novel approach to the treatment of the symptoms of schizophrenia. Curr Opin Invest Drugs 2007; 8: 54-59
  • 20 Reyes-Irisarri E, Markerink-Van Ittersum M, Mengod G et al. Expression of the cGMP-specific phosphodiesterases 2 and 9 in normal and Alzheimer’s disease human brains. Eur J Neurosci 2007; 25: 3332-3338
  • 21 Prickaerts J, Şık A, van der Staay FJ et al. Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation. Psychopharmacology (Berl.) 2005; 177: 381-390
  • 22 Rutten K, Vente JD, Şık A et al. The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in hippocampal slices. Behav Brain Res 2005; 164: 11-16
  • 23 Izquierdo I, Medina JH. Memory formation: the sequence of biochemical events in the hippocampus and its connection to activity in other brain structures. Neurobiol Learn Mem 1997; 68: 285-316
  • 24 Zhuo M, Hu Y, Schultz C et al. Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Nature 1994; 368: 635-639
  • 25 Barad M, Bourtchouladze R, Winder DG et al. Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc Natl Acad Sci USA 1998; 95: 15020-15025
  • 26 Bailey CH, Bartsch D, Kandel ER. Toward a molecular definition of long-term memory storage. Proc Natl Acad Sci USA 1996; 93: 13445-13452
  • 27 Frey U, Huang YY, Kandel ER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 1993; 260: 1661-1664
  • 28 Krause W, Kuhne G. Pharmacokinetics of rolipram in the rhesus and cynomolgus monkeys, the rat and the rabbit. Studies on species differences. Xenobiotica 1988; 18: 561-571
  • 29 van Staveren WC, Markerink-van Ittersum M, Steinbusch HW et al. The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat. Brain Res 2001; 888: 275-286
  • 30 Itoh T, Abe K, Tokumura M et al. Different regulation of adenylyl cyclase and rolipram sensitive phosphodiesterase activity on the frontal cortex and hippocampus in learned helplessness rats. Brain Res 2003; 991: 142-149
  • 31 Scott AI, Perini AF, Shering PA et al. ln-patient major depression: is rolipram as effective as amitriptyline. Eur J Clin Pharmacol 1991; 40: 127-129
  • 32 Dundore RL, Clas DM, Wheeler LT et al. Zaprinast increases cyclic GMP levels in plasma and in aortic tissue of rats. Eur J Pharmacol 1993; 249: 293-297
  • 33 Dundore RL, Habeeb PG, Pratt PF et al. Differential hemodynamic responses to selective inhibitors of cyclic nucleotide phosphodiesterases in conscious rats. J Cardiovasc Pharmacol 1992; 19: 937-944
  • 34 Cain DP. Testing the NMDA, long-term potentiation, and cholinergic hypotheses of spatial learning. Neurosci Biobehav Rev 1998; 22: 181-193
  • 35 Nagai T, Kamei H, Dohniwa M et al. Involvement of hippocampal extracellular signal-regulated kinase 1/2 in spatial working memory in rats. Neuroreport 2006; 17: 1453-1457
  • 36 Cheng 1 YF, Wang C, Lin HB et al. Inhibition of phosphodiesterase-4 reverses memory deficits produced by Aβ25-35 or Aβ1-40 peptide in rats. Psychopharmacology (Berl) 2010; 212: 181-191
  • 37 Wang 1 ZZ, Zhang Y, Liu YQ et al. RNA interference-mediated phosphodiesterase 4D splice variants knock-down in the prefrontal cortex produces antidepressant-like and cognition-enhancing effects. Br J Pharmacol 2013; 168: 1001-1014
  • 38 Zhang 1 H, Zhang SB, Zhang QQ et al. Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol. CNS Neurosci Ther 2013; 19: 484-493