3

2

1

*

A1 (L-Arg) (L-NAME)

NO (R-phenylisopropyladenosine=R-PIA) .

5

. 60 R-PIA . .

6

. 4 ( 4 )

30 L-Arg L-NAME . (open field) R-PIA 64/6 mg/kg

L-Arg . . R-PIA . R-PIA L-NAME

100 mg/kg

L-NAME 0/0625 -0/125 mg/kg L-Arg .

L-Arg L-NAME . . R-PIA L-NAME R-PIA .

.

R-PIA

:

-1 hosseinzadehh@mums.ac.ir 91775 -1365 : 0511 – 8823251 : : * -2 -3

(NO

)

.(11) .(4-1) ATP .(15) . -N ) .(16) ( -N- s) A2a) A1 .(11) L-NAME ( NO .(17) .(8 7) -L NO NOS . .(18) ( -N LTP (10) -D ) -L .(11) NO (L-NAME) (9 ) ) ) Long Term Potentiation=LTP .(6) ( A1 .(1) . CNS A3 A2 (A2b .(5)

(NOS (Step-down NO

)

LTP .(14)

NO (R-phenylisopropyladenosine) (L-NAME) (L-Arg) .

A1

LTP L-Arg-NO (1992) Rose NO Holster .(12) NO L-Arg NO .(13) NO NO ( .(14)

(rat) 250-300 6 12 • .

)

. .
(22) (Open field test)

23 .
(19)

2

. Morris water maze 30 . 25 . 20× 20 . . : . 16 9 . . ) 5 4 (Central) (Total) ( ) . . . . ( :Grooming :Rearing : Leaning : Defecation . ± ANOVA p< 0/05 . . Tukey – Kramer 30 . 60 PIA (R-phenylisopropyladenosine) . (L(21) . 30 (L-Arg) (20) NAME) . 30 . 90 ) . ( 4 . 5 100 × 100 60 136 25 . 10 20 1

:Locomotion
(Periphral) . (

.

)

N o r m al Salinn e Normal S al i R - P IA 0.06255 mg/kgg R-PIA 0 .0 6 2 m g /k R - P IA 0.125 mg/kg g R-PIA 0 .1 2 5 m g / k L - N A M E 100 mg/kg g L-NAME 1 0 0 m g / k L - N A M E 100 mg/kg+R-PIA 0.0625 2 5 m g / k g L-NAME 1 0 0 m g / k g + R - P IA 0 .0 6 mg/kg L - N A M E 100 mg/kg+L-Arg 64.6 mg/kg/k g L-NAME 1 0 0 m g / k g + L - Ar g 6 4 .6 m g L - A r g 64.6 mg/kg+R-PIA 0.0625 2 5 m g / k g L-Arg 6 4 .6 m g / k g + R - P IA 0 .0 6 mg/kg L - A r g 64.6 mg/kg g L-Arg 6 4 .6 m g / k 30 Latency Time (Sec) *** 20 * ***

0/0625 -0/125 mg/kg

R-PIA

.(2 1

) L-NAME

100mg/kg 64/6 mg/kg L-Arg .

10

0

R-PIA L-NAME L-Arg

:2

.(2 1

)

R-PIA L-NAME

NNormal Salin orm S e al alin
+ Tukey-Kramer . . 6

*** p< 0/05 *p< 0/001:

(Open field activity) R-PIA .(3 ) ( )

100

Normal Salin Normal Saline R-PIA 0.0625 mg/kg R-PIA 0.0625 mg/kg R-PIA 0.125 mg/kg R-PIA 0.125 mg/kg L-NAME 100100 mg/kg L-NAME mg/kg L-NAME 100100 mg/kg+R-PIAmg/kg mg/kg L-NAME mg/kg+R-PIA 0.0625 0.0625 L-NAME 100100 mg/kg+L-Arg 64.6 mg/kg L-NAME mg/kg+L-Arg 64.6 mg/kg L-Arg 64.6 mg/kg+R-PIA 0.0625mg/kg mg/kg L-Arg 64.6 mg/kg+R-PIA 0.0625 L-Arg 64.6 mg/kg L-Arg 64.6 mg/kg
75

Latency Time (Sec)

75

g R R-PIA 0.0625g/k -PIA0.0625m mg/kg g R R-PIA 0.125g/k -PIA0.125mmg/kg g L L-NAME 100g/k -N M 100m mg/kg AE L-NAME 100 mg/kg+R-PIA 0.0625 mg/kg g/k L A E100m g+R 0.0625m g -N M g/k -PIA g L L-NAME 100g/k -A 64.6m mg/kg -N M 100m mg/kg+L-Arg 64.6g/k AE g+L rg L-Arg 64.6g/k -PIA 0.0625 mg/kg mg/kg+R-PIA g/k L rg64.6m g+R 0.0625m g -A g L L-Arg 64.6g/k -A 64.6mmg/kg rg

50

25
Number of Entrance 50 *** *** 25 *** *** *** *** *** ***

0 0
CL

1

2

3 D ay Day

4

5

6

0 TL PL

R-PIA L-NAME L-Arg Locomotion . Total=TL Periphral=PL Central=CL ) . 6 : ( + ,Tukey-Kramer ) .

:3

R-PIA L-NAME L-Arg 5 + . (

:1

. 6

. .*** p< 0/001

.(2

)

. Posterior singulate LTD LTP A1 ) . ) DPCPX LTP A1 .(6) (R-PIA A2 A1 .(4) A1 .(23) GABA
R-PIA L-NAME L-Arg :4

L-Arg L-NAME .(4 3 )

)

. ( (%100 A1 A
15

.(4
Normal Salin Normal Saline R-PIA 0.0625 mg/kg R-PIA 0.0625 mg/kg R-PIA R-PIA 0.125 mg/kg0.125 mg/kg L-NAME L-NAME 100 mg/kg 100 mg/kg L-NAME 100 mg/kg+R-PIA 0.0625 mg/kg L-NAME 100 mg/kg+R-PIA 0.0625 mg/kg L-NAME 100 mg/kg+L-Arg 64.6 mg/kg L-NAME 100 mg/kg+L-Arg 64.6 mg/kg L-Arg 64.6 0.0625mg/kg L-Arg 64.6 mg/kg+R-PIAmg/kg+R-PIA 0.0625 mg/kg L-Arg L-ARG 64.6 mg/kg64.6 mg/kg

)
10 Number

.

NO NO

5 * *** ** *

*** *** *** ***

* ** ** *** * **

0 Rearing Leaning Grooming Defecation

NO NO . NO .(24) NO ATP A3 A2 A1 A1

.
: Leaning :Defecation 6 +

:Grooming .(Open-field test) : Rearing .

. .

,Tukey-Kramer

.** p< 0/01 ***p< 0/001 *p<0/05 :

NO .(25) R-PIA L-NAME NO R-PIA . . R-PIA L-Arg R-PIA . L-Arg R-PIA L-NAME . A1 L-NAME

CL/TL (NO) Grooming . grooming R-PIA .(22) L-Arg NOS grooming . leaning (GABA) L-NAME leaning L-Arg . A1 NO . .(28) grooming grooming . . A1 .(23) leaning grooming grooming .(27 26) .(23) grooming L. NO . NO NO R-PIA L-Arg Arg

References
Hosseinzadeh H, Stone Tw. Adenosine in the central nervous system. MJIRI. 9: 361-368. Prast H, Philippu A. Nitric oxide as modulator of neuronal function. Prog Neurobiol 2001; 64: 51– 68. Sawynok J. Adenosine and ATP receptors. Handb Exp Pharmacol 2007; 177: 309-328. Wei MH, Khoo HE, Ngoi SS, Moochhala S. Effects of adenosine receptor agonists on nitric oxide release in mouse during endotoxemia. Biochem Pharmacol 1995; 50: 45-47. 5. Stone TW. Purine receptors and their pharmacological roles. Advances in Drug Research. London: Academic Press 1989. 6. Pereira GS, Souza TME, Vinade ERC, Choi H, Rodrigues C, Battastini AMO, Izquierdo I, Sarkis JJF, Bonan CD. Blockade of adenosine A1 receptors in the posterior cingulated cortex facilitaes memory in rats. Eur J Pharmacol 2002; 437: 151-154. 7. Wang JH, Ma YY, van den Buuse, M. Improved spatial recognition memory in mice lacking adenosine A2A receptors. Exp Neurol 2006; 199: 438-445. 8. Zhang DS, Ren LM, Zhang L. Effects of adenosine A1 receptor antagonist on memory and its relationship with cholinergic nerve. J Chin Pharmac Univ 2006; 37: 63-66. 9. Bohm GA, Bon C, Stutzmann JM, Doble A, Blanchard JC. Possible involvement of nitric oxide in long-term potentiation. Eur J Pharmacol 1991; 199: 379-381. 10. Iga Y, Yoshioka M, Togashi H, Saito H. Inhibitory action of N-Omega-nitro-L-arginine methyl ester on in vivo long term potentiation in the rat dentate gyrus. Eur J Pharmacol 1993; 238: 395-398. 11. Baratti CM, Kopf SR. A nitric oxide synthase inhibitor impairs memory storage in mice. Neurobiol Learn Mem 1996; 65: 197-201. 12. O'Dell TJ, Hawkins RD, Kandel LR, Arancio O. Test of the rok of two diffusible Substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proceed Nat Academy Sci USA, 1991; 88: 11285-11289. 1. 2. 3. 4.

13. Holscher C, Rose SPR. An inhibitor of nitric oxide synthesis prevents memory formation in the chick.Neurosci Let, 1992; 145: 165-167. 14. Bohn GA, Bon C, Lemair M, Reibaud M, Piot O, Stutzmann JM, Double A, Blanchard JC. Altered synaptic plasticity and memory formation in nitric oxide synthase inhibitor-treated rats. Proc Nati Acad Sci USA 1993; 90: 9191-4. 15. Richard NS, NG NT, Gibbs ME. Nitric oxide agonist stimulates consolidsation of long-term memory in the 1-day old chick. Behav Neuroscience 1994; 108: 3-6. 16. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992; 6: 3051-3064. 17. Estall LB, Grant SJ, Cicala GA. Inhibition of nitric oxide (NO) production selectively impairs learning and memory in the rat. Pharmacol Biochem Behav 1993 ; 46: 595-562. 18. Brenna PA, Kishimoto J. Local inhibition of nitric oxide synthase activity in the accessory olfactory bulb dose not prevent the formation of an alfactory memory in mice, Brain Res 1993; 619: 306-312. 19. Nakagawa Y, Takashima T. The GABAB receptor antagonist CGP36742 attenuates the baclofen-an scopolamine-induced deficit in Morris water maze task in rats. Brain Res 1997; 766: 101-106. 20. Zarrindast MR, Iraie F, Heidari MR, Mohagheghi-Badi M. Effect of adenosine receptor agonists and antagonists on morphine-induced catalepsy in mice. Eur J Pharmacol 1997; 338:11-16. 21. Uzbay IT, Erden BF, Sever B, Kayaalp SO. L-arginine inhibits audiogenic seizures in ethanol withdrawn rats. Eur Neuropsychopharmacol 1995; 5: 398-399. 22. Pardon MC, Diaz FP, Joubert C, Salmon CC. Age-dependent effects of a chronic ultramild stress procedure on open-field behavioour in B6D2F1 femal mice. Physiol Behav 2000; 70: 7-13. 23. Kuroka WA, Shiozaki S, Nonaka H, Kase H, Nakamura J, Kuwana Y. In vivo regulation of acetylcholine release via adenosine A1 receptor in rat cerebral cotex. Neuroscience Let 1996; 209: 181-184. 24. Barcellos CK, Bradly PM, Burns BD, Webb AC. Effects of nitric oxide release in an erea of the chick forebrain which is essential for early learning. Dev Brain Res 2000; 121: 79-87. 25. Lawewncw AJ, Krstew E, Jarrott B. Complex intraction between nitric oxide and adenosine receptors in the rat isolated ganglion. Eur J Pharmacol 1997; 328: 83-88. 26. Alexander SPH, Losinski A, Kendall DA, Hill SJ. A comparison of A2 adenosine receptor stimulated cyclic AMP generation in cerebal cortex and relaxation of pre-contracted aorta. Br J Pharmacol 1994; 111: 185-190. 27. Celik T, Zagli U, Kayir H, Uzbay IT. Nitric oxide synthase inhibition blocks amphetamine-induces locomotor activity in mice. Drug Alcohol Dependence 1999; 56: 109-113. 28. Hosaja MJ, Venault P, Tobin C, Joubert C, Delocour J, Chapouthier G. Involvment of adrenal medulla grafts in the open-field behavior. Behav Brain Res 2001; 121: 29-37.