There is growing evidence that noradrenergic inputs to the prefrontal cortex (PFC) play an important role in regulating its function. This paper reviews the pharmacological control of noradrenaline (NA) release in this region, with particular reference to our studies using brain microdialysis, and also describes how NA levels are modulated by antidepressant and antipsychotic drugs. The suggestion that atypical antipsychotics such as clozapine and risperidone may produce clinical benefits by their ability to increase NA release is discussed. Finally, a new class of drugs, which show selectivity for imidazoline receptors is described. These compounds are shown to similarly increase extracellular NA in the PFC. Their potential utility as clinical treatments is discussed.
Carpéné C., Collon P., Remaury A., Cordi A., Hudson A., Nutt D.J., Lafonton M. (1995) Inhibition of amine oxidase activity by derivatives recognizing I2-imidazoline sites. J. Pharmac Exp Ther272: 681-688
2.
Charney D.S., Deutch AY, Krystal J.H., Southwick S.M., Davis M. (1993) Psychobiological mechanisms of post-traumatic stress disorder. Arch Gen Psychiat50: 294-305
3.
Dennis T., L'Heureux R., Carter C., Scatton B. (1987) Presynaptic alpha-2 adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline release. J Pharmac Exp Ther241: 642-649
4.
De Vos H., Convents A., De Keyser J., De Backer J., Van Megen I J B, Ebinger G., Vauquelin G. (1991) Autoradiographic distribution of α2-adrenoceptors, NAIBS and 5HT1A receptors in human brain using [3H]idazoxan and [3H]rauwolscine. Brain Res566:13-20
5.
Ernsberger P. (1992) Heterogeneity of imidazoline binding sites: proposed I1 and I2 subtypes. Fund Clin Pharmacol , 6, (Suppl. 1) P18
6.
Freedman J.E., Aghajanian G.K. (1984) Idazoxan (RX 781094) selectively antagonizes a2-adrenoceptors on rat central neurons. Eur J Pharmac105: 265-272
7.
French N., Lalies M.D., Nutt D.J., Pratt J.A. (1995) Idazoxan-induced reductions in cortical glucose use are accompanied by an increase in noradrenaline release: complementary [14C]2-deoxyglucose and microdialysis studies. Neuropharmacology34: 605-613
8.
Garcia-Sevilla JA, Escriba PV, Sastre M., Walzer C., Busquets X., Jaquet G., Reis DJ, Guimon J. (1996) Immunodetection and quantification of imidazoline receptor proteins in platelets of patients with major depression and in brains of suicide victims. Arch Gen Psychiat53: 803-810
9.
Gartside S.E., Umbers V., Hajos M., Sharp T. (1995) Interactions between a selective 5-HT1A receptor antagonist and an SSRI in vivo: effects on 5-HT cell firing and extracellular 5-HT. Br J Pharmac115:1064-1070
10.
Ghika J., Tennis M., Hoffman BA, Schoenfeld D., Growden J. (1991) Idazoxan treatment in progressive supranuclear palsy. Neurology41: 986-991
11.
Glue P., Costello MJ, Pert A., Mele A., Nutt DJ ( 1990) Regional neurotransmitter responses after acute and chronic electroconvulsive shock. Psychopharmacology100: 64-65
12.
Green AR (1990) The effects of antidepressant drugs on noradrenergic receptor mechanisms in the central nervous system. In Heal DJ, Marsden CA (eds), The pharmacology of noradrenaline in the central nervous system. Oxford University Press, Oxford, pp. 316-348
13.
Holets V.R. (1990) The anatomy and function of noradrenaline in the mammalian brain. In Heal, DJ, Marsden CA (eds), The pharmacology of noradrenaline in the central nervous system. Oxford University Press , Oxford, pp. 1-40
14.
Hudson A.L., Husbands S., Lewis J.W., Nutt D.J. (1994) Affinity and selectivity of BU224 and BU239 for rabbit brain non-adrenoceptor idazoxan binding sites (I2-sites) . Br J Pharmac112: 320P
15.
Lione LA, Nutt DJ, Hudson AL (1995) Characterisation and autoradiographical localization of imidazoline-2 (I2) sites labelled by [3H]2-(-2-benzofuranyl)-2-imidazoline in rat brain. Br J Pharmac116: 338P
16.
Lione L., Nutt DJ, Hudson A. (1996) [3H]-(2-Benzofuranyl)-2-imidazoline : a new selective high affinity radioligand for the study of rabbit brain imidazoline I2 receptors. Eur J Pharmac304: 221-229
17.
Litman R.E., SuT P., Potter W.Z., Hong W.W., Pickar D. (1996) Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia. Br J Psychiat168: 571-579
18.
L'Heureux R., Dennis T., Curet O., Scatton B. (1986) Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission. J Neurochem46: 1794-1801
19.
MacKinnon AC, Parnes H., Brown CM (1995) [3H]-RS-45041-190, a potent and selective radioligand for I2 imidazoline receptors. Br J Pharmac98: 1729-1736
20.
Mallard NJ, Hudson A.L., Nutt D.J. (1992) Characterisation and autoradiographic localization of non adrenoceptor binding sites in the rat brain. Br J Pharmac106:1019-1027
21.
Nutt D.J. (1994) Putting the 'A' in atypical: does α2-adrenoceptor antagonism account for the therapeutic advantage of new antipsychotics. J Psychopharmac8(4): 193-195
22.
Nutt D.J., Glue P. ( 1992) The neurobiology of ECT: animal studies. In: Coffey C E (ed.), ECT: from research to clinical practice. American Psychiatric Association, Washington DC, pp. 241-265
23.
Nutt D.J., Holman R.B., Thomas D.N. (1992) Noradrenergic mechanisms in anxiolytic and antidepressant drug action. In Elliott MJ (ed.), Experimental approaches to anxiety and depression. John Wiley, Chichester, pp. 101-106
24.
Nutt D.J., French N., Handley S., Hudson A., Husbands S., Jackson H.C., Jordan S., Lalies M.D., Lewis J.W., Lione L., Mallard N., Pratt J. (1995) Functional studies of specific imidazoline-2 receptor ligands. In Reis DJ, Bousquet P, Parini A (eds), The imidazoline receptor: pharmacology, functions, ligands and relevance to biology and medicine. New York Academy of Sciences, New York, pp.125-139
25.
Ordway G.A., Widdowson P.S., Smith K.S., Halaris A.E. (1994) Agonist binding to a2-adrenoceptors is elevated in the locus coeruleus from suicide victims. J Neurochem63: 617-624
26.
Parini A., Moudanos C.G., Pizzanat N., Lanier S.M. (1996) The elusive family of imidazoline binding sites . Trends Pharmac Sci17:13-16
27.
Pickar D., Owen D. ( 1992) Clinical and biological response to clozapine in patients with schizophrenia: crossover comparison with fluphenazine. Arch Gen Psychiat49: 345-353
28.
Piletz J.E., Slatten K.R., Halaris A.E. (1992) Imidazoline-preferring binding sites in human platelets: plasma membrane subtype I1 is elevated in mood disorders. Fund Clin Pharmac6 (Suppl. 1) : 11119
Routledge C., Marsden CA (1987) Comparison of the effects of selected drugs on the release of hypothalamic adrenaline and noradrenaline measured in vivo . Brain Res426: 103-111
31.
Stanford C., Nutt D.J. (1982) Comparison of the effects of repeated electroconvulsive shock on alpha2- and beta-receptors in different regions of rat brain. Neuroscience7: 1753-1757Stanford C., Nutt D.J., Cowen PJ (1983) Comparison of the effects of chronic desmethyl imipramine administration on alpha2 and beta adrenoceptors in different regions of rat brain. Neuroscience8: 161-164
32.
Thomas D.N., Holman R.B. (1991) A microdialysis study of the regulation of endogenous noradrenaline release in the rat hippocampus. J Neurochem56: 1741-1746
33.
Thomas D.N., Nutt DJ, Holman R.B. (1992) Effects of acute and chronic electroconvulsive shock on noradrenaline release in the rat hippocampus and frontal cortex. Br J Pharmac106: 430-434
34.
Thomas DN, Nutt DJ, Holman RB (1994) Regionally specific changes in extracellular noradrenaline following chronic idazoxan as revealed by in vivo microdialysis. Eur J Pharmac261 (1-2): 53-57
