Medial prefrontal cortex

Figure 7.5 Rate recording of the dose-dependent inhibitory effects of apomorphine (pg/kg) on the spontaneous activity of a neuron in the medial prefrontal cortex of the halothane anaesthetised rat and its antagonism by haloperidol (HAL, 0.5mg/kg). Time scale is 50 min intervals. Reproduced by permission from Dailey (1992)...

In other brain areas which receive a DA input, such as the nucleus accumbens and prefrontal cortex, it appears to be inhibitory and predominently D2-mediated. This is clear from Fig. 7.5 which shows inhibition by apomorphine (mixed D2, Di agonists) of the firing of neurons in the medial prefrontal cortex of the anaesthetised rat and its antagonism by the D2 antagonist haloperidol. 

To some extent, this proposal is supported by microdialysis studies of changes in 5-HT efflux in the terminal fields of 5-HT neurons. For instance, increased 5-HT efilux in the striatum, induced by immobilisation of rats, occurs only during the period of increased motor activity that follows the animals release (Takahashi et al. 1998). A single swim stress also fails to increase 5-HT efflux in the medial prefrontal cortex of rats. 

Both amphetamine and cocaine have also been reported to support intracranial self-administration in the mesolimbic/mesocortical dopaminergic system. Rats will self-administer cocaine into the medial prefrontal cortex (Goeders and Smith 1983). while amphetamine is self-administered into the orbitofrontal cortex of rhesus monkeys (Phillips and Rolls 1981) and the nucleus accumbens of rats (Hoebel et al. 1983 Monaco et al. 1981). These data indicate that the mesolimbic/mesocortical dopaminergic system is involved in the initiation of stimulant reinforcement processes, and this work suggests that the region of the nucleus accumbens, more specifically the mesolimbic dopamine system, may be an important substrate for reinforcing properties of several psychomotor stimulant drugs. 

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Middleton, L.S., Cass, W.A., and Dwoskin, L.P., Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex, J. Pharmacol. Exp. Then, 308, 367, 2003. 

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Other abnormalities are more trait-like, and persist following symptom remission. They are found in orbital and medial prefrontal cortex areas where postmortem studies have also documented reductions in cortex volume and histopathologic changes in primary mood disorders [68], Evidence from brain mapping, lesion analysis and electrophysiologic studies of humans and experimental... 

Milad, M. R. and Quirk, G. J. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420 70-74, 2002. 

Gessa GL, Casu MA, Carta G, Mascia MS. (1998). Cannabinoids decrease acetylcholine release in the medial-prefrontal cortex and hippocampus, reversal by SR 141716A. Eur J Pharmacol. 355(2-3) 119-24. 

Enrico P, Bouma M, de Vries JB, Westerink BH. 1998. The role of afferents to the ventral tegmental area in the handling stress-induced increase in the release of dopamine in the medial prefrontal cortex a dual-probe microdialysis study in the rat brain. Brain Res 779(1-2) 205-213. 

Hildebrand BE, Nomikos GG, Hertel P, SchEstrom B, Svensson TH. 1998. Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779(1—2) 214-225. 

Phillips AG, Ahn S, Lloresco SB. 2004. Magnitude of dopamine release in medial prefrontal cortex predicts accuracy of memory on a delayed response task. J Neurosci 24(2) 547-553. 

Taber MT, Fibiger HC. 1993. Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum. Neuropsychopharmacology 9(4) 271-275. 

Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24 1161-1192 Medina JF, Christopher RJ, Mauk MD, LeDoux JE (2002) Parallels between cerebellum- and amygdala-dependent conditioning. Nat Rev Neurosci 3 122-131 Milad MR, Quirk GJ (2002) Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420 70-74... 

Many patients with anxiety disorders experience an increased susceptibihty to psychosocial stress. Behavioral sensitization may account for these cHnical phenomena, hi the laboratory model of sensitization, single or repeated exposure to physical stimuU or pharmacological agents sensitizes an animal to subsequent stressors (reviewed in Charney et al. 1993). For example, in animals with a history of prior stress, there is a potentiated release of NE in the hippocampus with subsequent exposure to stressors (Nisenbaum et al. 1991). Similar findings were observed in medial prefrontal cortex (Finlay and Abercrombie 1991). The hypothesis that sensitization is underlying neural mechanism contributing to the course of anxiety disorders is supported by clinical studies demonstrating that repeated exposure to traumatic stress is an important risk factor for the development of anxiety disorders, particularly PTSD (Table 1). 

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Przbyslawski J, Roullet P, Sara SJ (1999) Attenuation of emotional and nonemotional memories after their reactivation role of p adrenergic receptors. J Neurosci 19 6623-6628 Quirk GJ, Russo GK, Barron JL, Lebron K (2000) The role of ventral medial prefrontal cortex in the recovery of extinguished fear. J Neurosci 20 6225-6231 Rasmussen K, Marilak DA, Jacobs BL (1986) Single unit activity of the locus coeruleus in the freely moving cat. 1. Dming naturalistic behaviors and in response to simple and complex stimuli. Brain Res 371 324-334... 

Marek, G.J. and Aghajanlan, G.K. (1999) 5-HT2A receptor or al-phal-adrenoceptor activation Induces EPSCs In layer V pyramidal cells of the medial prefrontal cortex. Eur ] Pharmacol 367 197-206. 

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