Chronic phenylethylamine stereotypy in rats: A new animal model for schizophrenia?

Borison, Richard L.; Havdala, H. S.; Diamond, Bruce I.

doi:10.1016/0024-3205(77)90431-3

Cited by 97 publications

(19 citation statements)

References 19 publications

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“…1A). DEP also induces stereotypy (Safta et al 1976), and as with locomotion, after treatment is stopped for 1 day, the stereotypic response returns to baseline, a result similar to that observed after chronic treatment with amphetamine (Borison et al 1977). This is the first report showing that, like DEP and amphetamine (Safta et al 1976), PHEN20 and BUP30 also induce head-weaving stereotypy (Fig.…”

Section: Locomotion and Stereotypysupporting

confidence: 74%

D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell

Kalyanasundar

Pérez

Luna

et al. 2015

Journal of Neurophysiology

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R. D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell. J Neurophysiol 114: 585-607, 2015. First published May 13, 2015 doi:10.1152/jn.00012.2015.-Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to shortterm treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.

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Section: Locomotion and Stereotypysupporting

confidence: 74%

D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell

Kalyanasundar

Pérez

Luna

et al. 2015

Journal of Neurophysiology

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“…The modulation of the GIRK channels by TAs might have a profound impact on integrative functions of the dopaminergic neurons to reduce the postsynaptic hyperpolarization caused by GABA released at inhibitory synapses. This suggests the involvement of trace amines in processes regulating motion, emotion, and reward (Borison et al, 1977;Sabelli et al, 1978;Wise and Bozarth, 1987;White, 1996). In particular, the shaping of GABA inputs could be an important phenomenon for the development of addiction, because it has been demonstrated recently that drugs of abuse alter GABA B receptor transmission in the ventral midbrain (Giorgetti et al, 2002) and activate TA receptors (Borowsky et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Trace Amines Depress GABAB Response in Dopaminergic Neurons by Inhibiting G-βγ-Gated Inwardly Rectifying Potassium Channels

Federici

Geracitano²,

Tozzi

et al. 2005

Molecular Pharmacology

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Trace amines (TAs) are present in the central nervous system in which they up-regulate catecholamine release and are implicated in the pathogenesis of addiction, attention-deficit/hyperactivity disorder, Parkinson's disease, and schizophrenia. By using intracellular and patch-clamp recordings from dopaminergic cells in the rat midbrain slices, we report a depressant postsynaptic action of two TAs, ␤-phenylethylamine (␤-PEA) and tyramine (TYR) on the GABA B -mediated slow inhibitory postsynaptic potential and baclofen-activated outward currents. ␤-PEA and TYR activated G-proteins, interfering with the coupling between GABA B receptors and G-␤␥-gated inwardly rectifying potassium channels. This is the first demonstration that ␤-PEA and TYR depress inhibitory synaptic potentials in neurons of the central nervous system, supporting their emerging role as neuromodulators.

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“…Although early neurobiologic models emphasized primary perturbations in striatolim bic dopamine (DA) activity to account for the therapeu tic effects of antidopaminergic drugs (Borison et al 1977;Kornetsky and Markowitz 1978;Kokkinidis and Anis man 1980;McKinney and Moran 1981), they did not represent potentially explanatory mechanisms for ei ther the cortical deftcits (Buchsbaum et al 1982;Wein berger et al 1986;Goldberg et al 1991;Berman and 0893-133X/93/$0.00 or the postpubertal onset that also characterize this illness. The subsequent discovery that the prefrontal cortex could regulate subcortical DA ac tivity (Pycock et a1.…”

Section: Jmentioning

confidence: 99%

Postpubertal Emergence of Hyperresponsiveness to Stress and to Amphetamine after Neonatal Excitotoxic Hippocampal Damage: A Potential Animal Model of Schizophrenia

Lipska¹,

Jaskiw²,

Weinberger³

1993

Neuropsychopharmacol

656

451

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The constellation of major phenomena associated with schizophrenia (e.g., postpubertal onset, congenital hippocampal area damage, cortical functional deficits, limbic dopamine (DA) dysregulation, and vulnerability to stress) have been difficult to explain with a unitary animal model. Although it has been shown that rats develop increased mesolimbic DA transmission and reduced cortical DA turnover following adult excitotoxic lesions of the ventral hippocampus (VH), the implications of early developmental VH lesions are not known. To determine the developmental sequelae of such changes, we produced ibotenic acid lesions of the ventral hippocampal formation in rats on the 7th day after birth (PD7). Motor activity in a novel environment, after saline injection and after d-amphetamine administration were similar in control and lesioned rats at PD35. However, in early adulthood, at PD56, animals with the hippocampal lesion were hyperactive in each of these conditions. The emergence of the hyperactivity at PD56 could be prevented by pretr�atment with haloperidol. Moreover, rats lesioned as nlion.(tes, in contrast to a similar lesion induced in adult animals, were also hyperresponsive to stress evaluated with a swim test. This latter effect is analogous to that seen after adult lesions of the medial prefrontal cortex, rather than after adult lesions of VH, suggesting that the neonatal VH lesion may affect functional development of the medial prefrontal cortex. These results demonstrate that in rats with neonatally induced excitotoxic VH lesions, behavioral indices consistent with increased mesolimbic DA responsivity to stressful and to pharmacologic stimuli emerge only in early adulthood. Homologous mechanisms may underlie certain aspects of the pathophysiology of schizophrenia. fNeuropsychopharmacology 9:67-75, 1993J

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Chronic phenylethylamine stereotypy in rats: A new animal model for schizophrenia?

Cited by 97 publications

References 19 publications

D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell

D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell

Trace Amines Depress GABAB Response in Dopaminergic Neurons by Inhibiting G-βγ-Gated Inwardly Rectifying Potassium Channels

Postpubertal Emergence of Hyperresponsiveness to Stress and to Amphetamine after Neonatal Excitotoxic Hippocampal Damage: A Potential Animal Model of Schizophrenia

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