Differential effects of selective dopamine, norepinephrine or catecholamine depletion on activity and learning in the developing rat

Raskin, Lisa A.; Shaywitz, Bennett A.; Anderson, George M.; Cohen, Donald J.; Teicher, Martin H.; Linakis, James G.

doi:10.1016/0091-3057(83)90073-4

Cited by 54 publications

(17 citation statements)

References 24 publications

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“…Converging literatures demonstrate that an aberrant DA circuitry and (or) defective noradrenergic function is associated with anxiety disorders (Mathew et al, 1981; Hamner and Diamond, 1996; Ballenger, 2001). Early studies on the neurobiology of active avoidance also focused on catecholamine systems (Beer and Lenard, 1975; Ashford and Jones, 1976; Fibiger and Mason, 1978; Oei and King, 1978; Raskin et al, 1983; Koob et al, 1984). In general, DA has mostly been implicated in the acquisition and expression of avoidance responses (Lenard and Beer, 1975; Fibiger and Mason, 1978) while NE may be more involved in the extinction of such responses (Lenard and Beer, 1975; Fibiger and Mason, 1978; Raskin et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

Effects of Psychotropic Agents on Extinction of Lever-Press Avoidance in a Rat Model of Anxiety Vulnerability

Jiao

Beck

Stewart

et al. 2014

Front. Behav. Neurosci.

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Avoidance and its perseveration represent key features of anxiety disorders. Both pharmacological and behavioral approaches (i.e., anxiolytics and extinction therapy) have been utilized to modulate avoidance behavior in patients. However, the outcome has not always been desirable. Part of the reason is attributed to the diverse neuropathology of anxiety disorders. Here, we investigated the effect of psychotropic drugs that target various monoamine systems on extinction of avoidance behavior using lever-press avoidance task. Here, we used the Wistar-Kyoto (WKY) rat, a unique rat model that exhibits facilitated avoidance and extinction resistance along with malfunction of the dopamine (DA) system. Sprague Dawley (SD) and WKY rats were trained to acquire lever-press avoidance. WKY rats acquired avoidance faster and to a higher level compared to SD rats. During pharmacological treatment, bupropion and desipramine (DES) significantly reduced avoidance response selectively in WKY rats. However, after the discontinuation of drug treatment, only those WKY rats that were previously treated with DES exhibited lower avoidance response compared to the control group. In contrast, none of the psychotropic drugs facilitated avoidance extinction in SD rats. Instead, DES impaired avoidance extinction and increased non-reinforced response in SD rats. Interestingly, paroxetine, a widely used antidepressant and anxiolytic, exhibited the weakest effect in WKY rats and no effects at all in SD rats. Thus, our data suggest that malfunctions in brain catecholamine system could be one of the underlying etiologies of anxiety-like behavior, particularly avoidance perseveration. Furthermore, pharmacological manipulation targeting DA and norepinephrine may be more effective to facilitate extinction learning in this strain. The data from the present study may shed light on new pharmacological approaches to treat patients with anxiety disorders who are not responding to serotonin re-uptake inhibitors.

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Section: Discussionmentioning

confidence: 99%

Effects of Psychotropic Agents on Extinction of Lever-Press Avoidance in a Rat Model of Anxiety Vulnerability

Jiao

Beck

Stewart

et al. 2014

Front. Behav. Neurosci.

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“…Pliszka et al (1996) and Arnsten et al (1996) have postulated a decreased noradrenergic function in ADHD. Depletion of NA in neonatal rats by administering 6-OHDA in combination with a selective DAT-inhibitor (Teicher et al 1986) has been shown to induce motor hyperactivity (Raskin et al 1983), learning deficits (Roberts et al 1976) and attention deficits (Carli et al 1983). The main source of central NA is the LC, which innervates the entire cerebral cortex, various subcortical areas, cerebellum and spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Animal models of attention deficit/hyperactivity disorder (ADHD): a critical review

Sontag

Tucha

Walitza

et al. 2010

ADHD Atten Def Hyp Disord

104

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Attention deficit/hyperactivity disorder (ADHD) involves clinically heterogeneous problems including attention deficits, behavioural hyperactivity and impulsivity. Several animal models of ADHD have been proposed, ranging from models with neurotoxic lesions to genetically manipulated animals. An ADHD model is supposed to show phenomenological similarities with the disorder, i.e. it should mimic the three core symptoms (face validity). A model should also conform to an established or hypothesized pathophysiological basis of the disorder (construct validity).Finally, an animal model should be able to predict previously unknown aspects of the neurobiology of ADHD or to provide potential new treatments (predictive validity). The currently proposed models are heterogeneous with regard to their pathophysiological alterations and their ability to mimic behavioural symptoms and to predict response to medication. This might reflect the heterogeneous nature of ADHD. Since the knowledge about the biology of ADHD from human studies is limited, one cannot at present decide which model best represents ADHD or certain ADHD subtypes. Animal models with good face and predictive validity may be useful for investigations of the underlying biological substrates of ADHD. At present, the models in use should be described as animal models of ADHD-like symptoms rather than models of ADHD.

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“…Dopaminergic afferent projections from the ventral tegmental area (VTA) to the cortex are the most frequently implicated pathways in neurodevelopmental disorders (Johnston et al, 1995;Berger-Sweeney and Hohmann, 1997;Benes et al, 2000). Experimental neonatal depletion of dopamine (DA) is known to result in behavioral deficits which include changes in locomotor activity (Miller et al, 1981;Kalsbeek et al, 1989a) and cognitive functions (Raskin et al, 1983;Archer et al, 1988;Pappas et al, 1992;Luthman et al, 1997). Notably, developmental DA deficits are associated with decreased cortical size and curtailed dendritic growth (Kalsbeek et al, 1987;1989b;Sherren and Pappas, 2005), in a fashion similar to the neuropathologic abnormalities reported in disorders thought to be secondary to altered DA homeostasis (Johnston et al, 1995;Shenton et al, 2001;Roth and Saykin, 2004).…”

Section: Introductionmentioning

confidence: 99%

Neonatal dopamine depletion induces changes in morphogenesis and gene expression in the developing cortex

et al. 2007

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The mesocorticolimbic dopamine (DA) system is implicated in mental health disorders affecting attention, impulse inhibition and other cognitive functions. It has also been involved in the regulation of cortical morphogenesis. The present study uses focal injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of BALB/c mice to examine morphological, behavioral and transcriptional responses to selective DA deficit in the fronto-parietal cortex. Mice that received injections of 6-OHDA on postnatal day 1 (PND1) showed reduction in DA levels in their cortices at PND7. Histological analysis at PND120 revealed increased fronto-cortical width, but decreased width of somatosensory parietal cortex. Open field object recognition suggested impaired response inhibition in adult mice after 6-OHDA treatment. Transcriptional analyses using 17K mouse microarrays showed that such lesions caused up-regulation of 100 genes in the cortex at PND7. Notably, among these genes are Sema3A which plays a repulsive role in axonal guidance, RhoD which inhibits dendritic growth and tubulin beta-5 microtubule subunit. In contrast, 127 genes were down-regulated, including CCT-epsilon and CCT-zeta that play roles in actin and tubulin folding. Thus, neonatal DA depletion affects transcripts involved in control of cytoskeletal formation and pathway finding, instrumental for normal differentiation and synaptogenesis. The observed gene expression changes are consistent with histological cortical and behavioral impairments in the adult mice treated with 6-OHDA on PND1. Our results point towards specific molecular targets that might be involved in disease process mediated by altered developmental DA regulation.

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Differential effects of selective dopamine, norepinephrine or catecholamine depletion on activity and learning in the developing rat

Cited by 54 publications

References 24 publications

Effects of Psychotropic Agents on Extinction of Lever-Press Avoidance in a Rat Model of Anxiety Vulnerability

Effects of Psychotropic Agents on Extinction of Lever-Press Avoidance in a Rat Model of Anxiety Vulnerability

Animal models of attention deficit/hyperactivity disorder (ADHD): a critical review

Neonatal dopamine depletion induces changes in morphogenesis and gene expression in the developing cortex

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