A NOVEL NON–RECEPTOR AND NON- GABAERGIC ANTIANXIETY-LIKE ACTIVITY OF FORSKOLIN: SYNERGY WITH DIAZEPAM


Ritu Malik, Neeraj Gilhotra

Abstract


Objective: Clinical problems associated with the benzodiazepines like dependence, withdrawal or tolerance may lead to under use of substances based on gamma-amino butyric acid (GABA). Non-GABAergic and substances that elevate cyclic adenosine monophosphate (cAMP) have shown anti-anxiety activity. Therefore, present investigation aimed to explore a non-GABAergic mechanism and non-receptor mediated anti-anxiety activity of a cAMP elevating agent, forskolin.

Methods: Elevated plus maze and light/dark box were employed to measure effect of forskolin on anxiety and the noted activity was compared with that of diazepam. cAMP levels were also measured in plasma of mice.

Results: Forskolin produced a significant antianxiety- like activity in unstressed mice and stressed mice. Diazepam produced a significant antianxiety- like activity in unstressed mice but not in stressed mice. The noted antianxiety activity of forskolin was accompanied by a significant elevation of cAMP levels.

Conclusions: The present findings contribute to suggest a non– receptor mediated anti-anxiety action of a forskolin, acting through cAMP elevation, thus avoiding receptor-mediated adverse effect profile of the conventional anxiolytics.

 


Keywords


cAMP, Anxiety, Forskolin, Stress

| PDF | HTML |

References


Korte SM, De Boer SF. A robust animal model of state anxiety: fear potentiated behaviour in the elevated plus maze. Eur J Pharmacol 2003;463:163-75.

Beer B, Chasin M, Clody DE, Voge JR, Horovitz ZR. Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety. Sci 1972;176:428–30.

Nibuya M, Nestler EJ, Duman SR. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996;16:2365–72.

Robello M, Amico C, Bucossi G, Cupello A, Rapallino MV, Thellung S. Nitric oxide and GABAA receptor function in the rat cerebral cortex and cerebellar granule cells. Neurosci 1996;74:99-105.

Skinner JE, Welch KMA, Reed JC, Nell JH. Psychological stress reduces cyclic 3',5'-adenosine monophosphate levels in the cerebral cortex of conscious rats, as determined by a new cryogenic method of rapid tissue fixation. J Neurochem 1978;30:691-8.

Chen C-C, Yang C-H, Huang C-C, Hsu K-S. Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity. Neuropsychopharmacol 2010;235:1605-17.

Silvestre JS, Fernandez AG, Palacios JM. Effects of rolipram on the elevated plus-maze test in rats: a preliminary study. J Psychopharmacol 1999;13:274–7.

Bersudsky Y, Kotler M, Shifrin M, Belmaker RH. A preliminary study of possible psychoactive effects of intravenous forskolin in depressed and schizophrenic patients. J Neural Transm 1996;103:1463–7.

Shindou T, Nonaka H, Richardson PJ, Mori A, Kase H, Ichimura M. Presynaptic adenosine A2A receptors enhance GABAergic synaptic transmission via a cyclic AMP dependent mechanism in the rat globus pallidus. Br J Pharmacol 2002;136:296–302.

Schwartz TL, Nihalani N, Simionescu M, Hopkins G. History repeats itself: pharmacodynamic trends in the treatment of anxiety disorders. Curr Pharm Des 2005;11:255–63.

Cherry JA, Thompson BE, Pho V. Diazepam and rolipram differentially inhibit cyclic AMP-specific phosphodiesterases PDE4A1 and PDE4B3 in the mouse. Biochim Biophys Acta-Gene Struct Expression 2001;1518:27–35.

Carceles MD, Ribὀ AR, Davalos R, Martinez T, Hernandez J. Effect of diazepam on adenosine 3’,5’-cyclic monophosphate (cAMP) plasma levels in anesthetized patients. Clin Ther 2004;26:737-43.

Kelley DJ, Bhattacharya A, Lahvis GP, Yin JC, Malter J, Davidson RJ. The cyclic AMP phenotype of fragile X and autism. Neurosci Biobehav Rev 2008;32:1533–43.

Saddock BJ, Saddock VA. In Kaplan and Saddock’s (eds): Pocket handbook of psychiatric drug treatment. Lippincott, USA: Williams and Wilkins; 2001.

Bartos J, Pesez M. Colorimetric and fluorimetric determination of steroids. Pure Appl Chem 1979;51:2157–69.

Calatayud F, Belzung C, Aubert A. Ethological validation and the assessment of anxiety-like behaviours: methodological comparison of classical analyses and structural approaches. Behav Processes 2004;67:195–206.

Madrigal JLM, Olivia HO, Moro MA, Lizasoain I, Lorenzo P, Castrillo A, et al. The increase in TNF-α Levels is implicated in NF-κB activation and inducible nitric oxide synthase expression in brain cortex after immobilization stress. Neuropsychopharmacol 2002;26:155–63.

Sevgi S, Ozek M, Eroglu L. L-NAME prevents anxiety like and depression-like behaviour in rats exposed to restraint stress. Methods Find Exp Clin Pharmacol 2006;28:95–9.

Goyal R, Kumar A. Protective effect of alprazolam in acute immobilization stress-induced certain behavioral and biochemical alterations in mice. Pharmacol Rep 2007;59:284–90.

Kumari B, Kumar A, Dhir A. Protective effects of non-selective and selective COX-2 inhibitors in acute immobilization stress induced behavioral and biochemical alterations. Pharmacol Rep 2007;59:699.

Gilhotra N, Dhingra D. Involvement of NO-cGMP pathway in anti-anxiety effect of aminoguanidine in stressed mice. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:1502–7.

Gilhotra N, Dhingra D. GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice. Brain Res 2010;1352:167–75.

Bhattacharya SK, Bhattacharya D. Effect of restraint stress on rat brain serotonin. J Biosci 1982;4:269–74.

Koyama S, Kubo C, Rhee JS, Akaike N. Presynaptic serotonergic inhibition of GABAergic synaptic transmission in mechanically dissociated rat basolateral amygdala neurons. J Physiol 1999;518:525-38.

Sharma V, Gilhotra R, Dhingra D, Gilhotra N. Possible underlying influence of p38MAPKinase and NF-kappaB in compromised effect of diazepam in stressed mice. J Pharmacol Sci 2011;116:257-63.

Sun AY, Li DX, Wang YL. Stress-induced changes of central GABAergic function in rats. Zhongguo Yao Li Xue Bao 1991;12:387–90.




About this article

Title

A NOVEL NON–RECEPTOR AND NON- GABAERGIC ANTIANXIETY-LIKE ACTIVITY OF FORSKOLIN: SYNERGY WITH DIAZEPAM

Keywords

cAMP, Anxiety, Forskolin, Stress

Date

19-12-2014

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 7, Issue 2, 2015 Page: 200-203

Online ISSN

0975-1491

Statistics

285 Views | 93 Downloads

Authors & Affiliations

Ritu Malik
Maharshi Dayanand University
India

Neeraj Gilhotra
Maharshi Dayanand University
India


Article Tools



Refbacks

  • There are currently no refbacks.