Defective Motor Behavior and Neural Gene Expression in RIIβ-Protein Kinase A Mutant Mice

Brandon, Eugene P.; Logue, Sheree F.; Adams, Martha; Qi, Ming; Sullivan, Sean P.; Matsumoto, Alvin M.; Dorsa, Daniel M.; Wehner, Jeanne M.; McKnight, G. Stanley; Idzerda, Rejean L.

doi:10.1523/jneurosci.18-10-03639.1998

Cited by 143 publications

(140 citation statements)

References 73 publications

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“…Nevertheless, given the critical role of PKA in the regulation of motor and emotive behavior, memory, stress and also in the action of psychotropic medications, the results we report may contribute to explain some of the clinical and pharmacological features of psychotic depression. 1,2,18,25,26 In conclusion, we found that the levels of PKA are altered in depressed patients with psychotic features. This study adds to the growing evidence suggesting that affective disorders with or without psychotic features might be associated with distinctive biochemical alterations of the cAMP signaling pathway.…”

Section: Figurementioning

confidence: 53%

cAMP signaling pathway in depressed patients with psychotic features

et al. 2002

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Abnormalities in protein kinase A (PKA) and Rap1 have recently been reported in depressed patients. The aim of the present study was to investigate the levels of these proteins in platelets from untreated unipolar and bipolar depressed patients with psychotic features. The levels PKA and Rap1 were assessed by Western blot analysis and immunostaining in 37 drug-free patients and 29 healthy subjects. Both unipolar and bipolar patients with psychotic depression have significantly lower levels of platelet regulatory type I and higher levels of catalytic subunits of PKA than controls, whereas the levels of regulatory type II were higher only in psychotic unipolar patients. No significant differences were found in the immunolabeling of both Rap1 and actin among groups. These findings support the idea that besides nonpsychotic depression, abnormalities of PKA could be linked, albeit in a somewhat different way, with psychotic depression. Molecular Psychiatry ( Several studies have shown that dysfunctions in PKA and some of its subtrates such as CREB and Rap1 are associated with affective disorders. 1-9 Delusional or psychotic depression is a severe disorder affecting approximately 20% of depressed patients and 0.6% of the general population. 10 According to DSM-IV criteria, it is defined by the presence of a major depressive episode accompanied by delusions and/or hallucinations that occurs in patients suffering from unipolar or bipolar disorder. 11 Although several biological differences were reported between psychotic and nonpsychotic depression, [12][13][14][15][16] there is at present no information on the possible involvement of the cAMP signaling pathway in psychotic depression. In this study we examined the levels of PKA and Rap1 in platelets from drugfree psychotic depressed patients and healthy subjects. We demonstrated that both unipolar and bipolar patients with psychotic depression have significantly lower levels of regulatory type I and higher levels of catalytic subunits of PKA than controls, whereas the levels of regulatory type II were higher only in unipolar patients. No significant differences were found in the immunolabeling of both Rap1 and actin among groups.These findings further support the idea that besides nonpsychotic depression, abnormalities of cAMP signaling pathway could be linked, albeit in a somewhat different way, with psychotic depression. The PKA subunits, Rap1 and actin were assessed by Western blot analysis, immunostaining and computerassisted imaging in whole platelet proteins from 37 drug-free depressed patients with psychotic features and 29 healthy subjects. Figure 1 illustrates representative immunoblots of regulatory type I (RI), type II (RII) and catalytic (C) subunits of PKA, Rap1 and actin in platelets from bipolar and unipolar patients with psychotic features and control subjects.As determined by the analysis of variance, the immunolabeling of the RI subunit of PKA was significantly different among groups (F 2,61 = 5.90; P = 0.004). Post hoc comparisons showed that both bi...

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Section: Figurementioning

confidence: 53%

cAMP signaling pathway in depressed patients with psychotic features

et al. 2002

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“…However, the reduction in the R subunits, albeit relatively modest, may explain alone or in combination with other dysfunctions, certain clinical and pharmacological features of schizophrenia. This hypothesis is supported by studies showing that PKA could play a key role in the regulation of motor and emotive behavior, memory, stress and also in the action of psychotropic medications (Abel et al 1997;Duman et al 1997;Adams et al 1997;Brandon et al 1998).…”

Section: Discussionmentioning

confidence: 77%

Abnormal Levels of cAMP-dependent Protein Kinase Regulatory Subunits in Platelets from Schizophrenic Patients

Tardito

Tura²,

Bocchio³

et al. 2000

Neuropsychopharmacology

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“…The R11 β-protein kinase A (PKA) isoform is highly expressed in mouse stratium and serves a role in dopamine receptor signaling. R11β-PKA mutant mice did not differ in acute locomotor response to amphetamine; however, they exhibited a larger magnitude of behavioral sensitization (Brandon et al, 1998). This suggests a role for this PKA isoform in behavioral neuroadaptation to amphetamine.…”

Section: Cell Support and Signaling Proteins: Amphetamine And Methamphementioning

confidence: 85%

Behavioral genetic contributions to the study of addiction-related amphetamine effects

Phillips

Kamens

Wheeler

2008

Neuroscience & Biobehavioral Reviews

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Amphetamines, including methamphetamine, pose a significant cost to society due to significant numbers of amphetamine-abusing individuals who suffer major health-related consequences. In addition, methamphetamine use is associated with heightened rates of violent and property-related crimes. The current paper reviews the existing literature addressing genetic differences in mice that impact behavioral responses thought to be relevant to the abuse of amphetamine and amphetaminelike drugs. Summarized are studies that used inbred strains, selected lines, single gene knockouts and transgenics, and quantitative trait locus (QTL) mapping populations. Acute sensitivity, neuroadaptive responses, rewarding and conditioned effects are among those reviewed. Some gene mapping work has been accomplished, and although no amphetamine-related complex trait genes have been definitively identified, translational work leading from results in the mouse to studies performed in humans is beginning to emerge. The majority of genetic investigations has utilized single-gene knockout mice and has concentrated on dopamine-and glutamate-related genes. Genes that code for cell support and signaling molecules are also well-represented. There is a large behavioral genetic literature on responsiveness to amphetamines, but a considerably smaller literature focused on genes that influence the development and acceleration of amphetamine use, withdrawal, relapse, and behavioral toxicity. Also missing are genetic investigations into the effects of amphetamines on social behaviors. This information might help to identify at-risk individuals and in the future to develop treatments that take advantage of individualized genetic information.

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Defective Motor Behavior and Neural Gene Expression in RIIβ-Protein Kinase A Mutant Mice

Cited by 143 publications

References 73 publications

cAMP signaling pathway in depressed patients with psychotic features

cAMP signaling pathway in depressed patients with psychotic features

Abnormal Levels of cAMP-dependent Protein Kinase Regulatory Subunits in Platelets from Schizophrenic Patients

Behavioral genetic contributions to the study of addiction-related amphetamine effects

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