Cortex frontal

The frontal cortex consists of three main structures (i) motoric regions (including the Broca area and ocular areas), (ii) the prefrontal cortex, and (iii) the orbital cortex. The prefrontal cortex is associated with attention, arousal, and expectation, the orbital cortex with motivation. 

Figure 4,7 The effect of perfusion of the microdialysis probe with a medium containing a depolarising (80 mM) concentration of K" ", or Ca +-free medium, for the periods indicated by the bars. The graph shows efflux of noradrenaline in the frontal cortex of anaesthetised rats. Increasing the concentration of K" " in the medium infused via the probe increases noradrenaline efflux whereas removing Ca reduces it...

Figure 4.8 Noradrenaline concentration in dialysis samples from probes implanted in the rat frontal cortex. Spontaneous efflux of noradrenaline is stable throughout a 4h sampling period ( extended basals ) but is increased markedly when either the noradrenaline reuptake inhibitor, desipramine (5 pM), or the a2-adrenoceptor antagonist, atipamezole (0.5 pM), is infused into the extracellular fluid via the microdialysis probe ( retrodialysis )...

Sharp, T, Umbers, V and Gartside, SE (1997) Effect of a selective 5-HT reuptake inhibitor in combination with 5-HTlA and 5-HTlB receptor antagonists on extracellular 5-HT in rat frontal cortex in vivo. Br. J. Pharmacol. 121 941-946. 

D4 Again very few in number compared with D2 but located in frontal cortex, midbrain and amygdala. High affinity for DA (Alj 20 nM) and a number of variants in humans. 

Many brain areas are innervated by neurons projecting from both the locus coeruleus and the lateral tegmental system but there are exceptions (Fig. 8.3). The frontal cortex, hippocampus and olfactory bulb seem to be innervated entirely by neurons with cell bodies in the locus coeruleus whereas most hypothalamic nuclei are innervated almost exclusively by neurons projecting from the lateral tegmental system. The paraventricular nucleus (and possibly the suprachiasmatic nucleus, also) is an exception and receives an innervation from both systems. 

Figure 8.11 Noradrenaline efflux, measured by microdialysis, in the rat frontal cortex and hypothalamus, (a) Repeated exposure to a tone, alone, has no effect on noradrenaline efflux in either brain region, (b) After repeated pairing of the tone with transfer of the rat to a brightly lit (aversive) arena, the sound of the tone alone triggers a significant ( P<0.05, cf last basal sample) increase in noradrenaline efflux in the frontal cortex, but not the hypothalamus. (Based on a figure from McQuade and Stanford 2000)...

McQuade, R and Stanford, SC (2000) A microdialysis study of the noradrenergic response in rat frontal cortex and hypothalamus to a conditioned cue for aversive, naturalistic environmental stimuli. Psychopharmacology 148 201-208. 

So far, little is known about this novel 5-HTid receptor but, in the rat and human, its mRNA is found, albeit in low concentrations, in the basal ganglia, nucleus accumbens, hippocampus, frontal cortex and Raphe nuclei. It is negatively coupled to adenylyl cyclase and is possibly located presynaptically, on both the 5-HT neuronal cell body and terminals, but this has yet to be confirmed. 

The 5-HT3 receptor is found appropriately in mesocortical areas and while behavioural studies with their antagonists in rodents showed potential antipsychotic activity, they have proved ineffective in patients. 5-HTia agonists may be more useful. They have been found to increase the extracellular concentration of DA in the frontal cortex of rats but diminish apomorphine-induced stereotypy (striatal effect). So they could be of some benefit, especially against negative symptoms, without causing EPSPs (see Chapter 9). 

These observations question the role of noradrenaline as an initiator of anxiety as does the finding that the anti-anxiety drug, buspirone (see Chapter 9), increases the concentration of noradrenaline in the extracellular fluid in the frontal cortex of freely-moving rats (Done and Sharp 1994). Whether this is because buspirone is metabolised to l-(2-pyrimidinyl)-piperazine (1-PP), which is an a2-adrenoceptor antagonist, is uncertain. Unfortunately, no studies have investigated the effects of chronic administration of this drug on noradrenergic transmission this could be important because, unlike benzodiazepines, buspirone is effective therapeutically only after several weeks of treatment. 

Dailey, JW, Mason, K and Stanford, SC (1996) Increased levels of extracellular noradrenaline in the frontal cortex of rats exposed to naturalistic environmental stimuli modulation by acute systemic administration of diazepam or buspirone. Psychopharmacology 127 47-54. 

Gobert, A, Rivet, JM, Cistarelli, L, Melon, C and Millan, MJ (1997) Alpha2-adrenergic receptor blockade markedly potentiates duloxetine- and fluoxetine-induced increases in noradrenaline, dopamine and serotonin levels in the frontal cortex of freely moving rats. J. Neurochem. 69 2616-2619. 

Cortisol concentration Plasma r ligands and allosteric coupling to high-affinity glycine sites (frontal cortex of suicides)... 

PAN Y, ANTHONY M, CLARKSON T B (1999a) Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats. Proc Soc Exp Biol Med. 221 118-25. 

We are routinely screening compounds for ability to displace 1-125 DOI from frontal cortex homogenates. As far as the CNS stimulant effects, differentiating from psychostimulants, the present model we are using is substitution in amphetamine-trained rats, in drug discrimination. We have used synaptosomes and looked at their effect on dopamine release and reuptake. But basically they are correlative models. 

The neuroehemical sites for psyehomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus aeeumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intraeranial self-administration of eoeaine is elicited from the frontal cortex, but not from the nucleus aeeumbens (Goeders and Smith 1983). Thus, eoneomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983 Smith et al. 1982). 

ANSWER No, I never tried that, but the literature there is complicated, as you know. Animals will, however, self-administer cocaine into the frontal cortex. Amphetamine is self-administered into the nucleus accumbens. 

Ryan, L.J. Tepper, J.M. Young, S.J. and Groves, P.M. Frontal cortex stimulation evoked neostriatal potentials in rats Intraeellular and extraeellular analysis. Brain Res Bull 17 751-758, 1986a. 

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