Substance P-immunoreactive neurons in the neocortex of the rat: A subset of the glutamic acid decarboxylase-immunoreactive neurons

Penny, G.R.; Afsharpour, Salman; Kitai, S.T.

doi:10.1016/0304-3940(86)90119-9

Cited by 70 publications

(14 citation statements)

References 11 publications

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“…In rat medial prefrontal cortex corresponding to the primate prelimbic area, large coarse SP containing fibers are present throughout layers II, III and IV [30]. Double labeling studies suggest the majority of SP positive cells also contain GABA and are likely to be part of a local inhibitory circuit [31]. While many of the SP positive fibers are likely to represent axons from neurons intrinsic to the rat cortex, several studies have raised the possibility that some fibers originate outside of the cortex, perhaps from the lateral tegmental nucleus adjacent to the locus coeruleus [32,33].…”

Section: Frontal Cortexmentioning

confidence: 95%

Do Substance P and the NK1 Receptor have a Role in Depression and Anxiety?

McLean¹

2005

CPD

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Research on Substance P (SP) has, until recently, focused on its role in pain and inflammation. However, a report that NK(1) receptor antagonists have utility in the treatment of depression has stimulated research into the function of SP and the NK(1)receptor in anxiety and depression. The distribution of SP and the NK(1) receptor in brain areas implicated in anxiety and depression is initially reviewed. This is followed by evaluation of the preclinical data obtained for SP and NK(1) receptor antagonists in behavioral models of depression as well as the phenotype of genetically modified animals lacking the genes encoding for the NK(1) receptor or for SP. The weight of the evidence supports antidepressant and anxiolytic activity of NK(1) receptor antagonists. However, many of the studies do not control for nonspecific effects of the compounds, and when enantiomers that lack activity at the NK(1) receptor are included, the results, in some cases, suggest that blockade of NK(1) receptors does not account for the observed behavioral activity. Finally, clinical studies in depressed patients assessing SP levels in plasma and cerebrospinal fluid as well as the effect of NK(1) receptor antagonists are reviewed. The clinical studies are a mixture of positive, failed and negative studies on the antidepressant activity of NK(1) receptor antagonists, not unlike the early clinical results obtained with selective serotonin reuptake inhibitors.

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Section: Frontal Cortexmentioning

confidence: 95%

Do Substance P and the NK1 Receptor have a Role in Depression and Anxiety?

McLean¹

2005

CPD

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“…SP-immunoreactive nerve fibres were also found in the rat cortex and hippocampus [16]. SPimmunoreactive neurons were sparsely distributed throughout the layers of the neocortex, and colocalization studies revealed that these cells were a subset of the glutamic acid decarboxylasecontaining, presumably GABA (γ amino butyric acid)-ergic, neurons [17]. Co-existence of SP with serotonin and GABA was also shown to occur in some neurons of the raphe nuclei of the rat medulla [18,19].…”

Section: Synthesis and Distribution Of Tachykinins In The Nervous Systemmentioning

confidence: 95%

Tachykinins and Neuropsychiatric Disorders

Chahl

2006

CDT

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The classical tachykinins, substance P, neurokinin A and neurokinin B are predominantly found in the nervous system where they act as neurotransmitters and neuromodulators. Their respective preferred receptors are NK1, NK2, and NK3 receptors. The presence of substance P in nociceptive primary afferent neurons, electrophysiological studies showing that it activated neurons in the dorsal horn of the spinal cord, and behavioral studies in animals, supported the concept that substance P was an important transmitter in the nociceptive pathway. It was therefore surprising that non-peptide NK1 receptor antagonists were ineffective as analgesics in clinical pain conditions. Nevertheless, the discovery that NK1 receptor antagonists had antidepressant activity led to renewed interest in these antagonists. It is disappointing that clinical trials of MK869 (aprepitant) for depression were suspended. The future of NK1 receptor antagonists as antidepressant drugs will depend on the outcome of clinical trials with other NK1 receptor antagonists. NK1 receptor antagonists were also found to be effective antiemetics, and aprepitant has recently become available for the treatment of chemotherapy induced emesis. Although less is known of the potential of NK2 and NK3 receptor antagonists, recent trials of NK3 receptor antagonists have shown efficacy in schizophrenia. The discovery of a new family of tachykinins, the hemokinins and endokinins, which acts on NK1 receptors and has potent effects on immune cells, has implications for the clinical use of NK1 receptor antagonists. Thus specific therapeutic strategies may be required to enable NK1 receptor antagonists to be introduced for treatment of neuropsychiatric disorders.

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“…Cocaine applied in vitro to septal slice preparations taken from animals treated chronically with cocaine reveals an increased number of cells showing hyperpolarizing rather than depolarizing responses (Shoji et al, 1998), suggesting that the compensatory upregulation of GABA A receptors shown here could lead to a reduction in excitatory responses to cocaine. Substance P is present in a subpopulation of cortical GABAergic interneurons (Penny et al, 1986) and acts at excitatory G-protein-coupled neurokinin-1 receptors (NK 1 ) within frontal cortex (Saffroy et al, 2003). Substance P-induced excitation of GABAergic interneurons after increased activation of cortical pyramidal neurons has been implicated in models of epilepsy, because substance P promotes the release of GABA within the entorhinal cortex and can attenuate epileptiform activity in this region (Maubach et al, 1998;Stacey et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

ΔFosB Induction in Orbitofrontal Cortex Mediates Tolerance to Cocaine-Induced Cognitive Dysfunction

Winstanley¹,

LaPlant²,

Theobald³

et al. 2007

J. Neurosci.

132

152

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Current cocaine users show little evidence of cognitive impairment and may perform better when using cocaine, yet withdrawal from prolonged cocaine use unmasks dramatic cognitive deficits. It has been suggested that such impairments arise in part through druginduced dysfunction within the orbitofrontal cortex (OFC), yet the neurobiological mechanisms remain unknown. We observed that chronic cocaine self-administration increased expression of the transcription factor ⌬FosB within both medial and orbitofrontal regions of the rat prefrontal cortex. However, the increase in OFC ⌬FosB levels was more pronounced after self-administered rather than experimenter-administered cocaine, a pattern that was not observed in other regions. We then used rodent tests of attention and decision making to determine whether ⌬FosB within the OFC contributes to drug-induced alterations in cognition. Chronic cocaine treatment produced tolerance to the cognitive impairments caused by acute cocaine. Overexpression of a dominant-negative antagonist of ⌬FosB, ⌬JunD, in the OFC prevented this behavioral adaptation, whereas locally overexpressing ⌬FosB mimicked the effects of chronic cocaine. Gene microarray analyses identified potential molecular mechanisms underlying this behavioral change, including an increase in transcription of metabotropic glutamate receptor subunit 5 and GABA A receptors as well as substance P. Identification of ⌬FosB in the OFC as a mediator of tolerance to the effects of cocaine on cognition provides fundamentally new insight into the transcriptional modifications associated with addiction.

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Substance P-immunoreactive neurons in the neocortex of the rat: A subset of the glutamic acid decarboxylase-immunoreactive neurons

Cited by 70 publications

References 11 publications

Do Substance P and the NK1 Receptor have a Role in Depression and Anxiety?

Do Substance P and the NK1 Receptor have a Role in Depression and Anxiety?

Tachykinins and Neuropsychiatric Disorders

ΔFosB Induction in Orbitofrontal Cortex Mediates Tolerance to Cocaine-Induced Cognitive Dysfunction

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