Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of cocaine to exert internal stimulus control of behavior was investigated by training rats to discriminate 10 mg/kg cocaine from saline in a discrete-trial, two-lever, food-reward procedure. Acquisition of response control by cocaine (1) succeeded in all animals tested, (2) proceeded rapidly, and (3) was associated with a high Commission Error: Omission Error ratio. These findings support the hypothesis that cocaine, a prototype of drugs inducing a psychotic condition in humans, can act as a powerful internal stimulus in rats. The cocaine cue was also responsive to the action of the dopamine-receptor-blocking agents spiperone (ED50: 0.06 mg/kg), haloperidol (0.24 mg/kg), and pimozide (1.90 mg/kg). d, l-Amphetamine (1.25 mg/kg) induced stimulus generalization with cocaine, and this generalization was blocked by dosages of the same neuroleptics comparable to those of cocaine antagonism. The results are discussed in terms of internal stimulus control of behavior and its relevance to the psychophysiology of schizophrenia.
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PMID:Neuroleptic interference with the cocaine cue: internal stimulus control of behavior and psychosis. 2 46

The model psychosis associated with amphetamine overdosage is known to bear a close resemblance to acute paranoid schizophrenia. Amphetamine is chemically similar to the endogenous sympathomimetic amine, phenylethylamine, which possess many of its pharmacological properties. It is suggested that some cases of schizophrenia may be associated with an abnormal phenylethylamine response, either from increased concentrations of the amine or from abnormal receptor sensitivity to it.
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PMID:Does phenylethylamine cause schizophrenia? 5 86

Amphetamine psychosis has been considered to be a pharmacologic model of schizophrenia. Fifteen previously reported cases were reviewed in which experimental induction of amphetamine psychosis occurred in nonschizophrenic drug abusers. Seven (possibly ten) cases manifested Schneider's first rank symptoms and all had World Health Organization Present-State Exam symptoms which discriminated schizophrenia. This observation draws further parallels between the phenomenology of amphetamine psychosis and schizophrenic symptoms.
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PMID:Amphetamine psychosis and psychotic symptoms. 11 94

Amphetamine-induced stereotyped behavior in animals is proposed as a model for schizophrenia. Chronic amphetamine administration produces stereotyped behavior and a paranoid schizophreniform syndrome in man, whereas in animals a behavioral sensitization to stereotypy is evoked. We now show that phenylethylamine (PEA), an amphetamine-like stimulant concentrated in the limbic system of human brain, produces stereotypy in rats with a behavioral sensitization when chronically administered. In comparing amphetamine-induced stereotypy with PEA-induced stereotypy, we found that the alpha-adrenergic blocking agents phentolamine and phenoxybenzamine selectively antagonize PEA stereotypy, whereas the beta-adrenergic blocking agent propranolol fails to alter significantly stereotypies evoked by PEA or amphetamine administration. Catecholamine depletion by alpha-methyl-p-tyrosine administration blocks stereotypies induced by both PEA amphetamine, whereas selective norepinephrine depletion antagonizes only PEA stereotypy; the amino acid precursors of both norepinephrine and dopamine potentiate stereotypies. Therefore, PEA-elicited stereotypy, but not amphetamine-elicited stereotypy, is dependent upon norepinephrine; the significance of this for the PEA animal model of schizophrenia is discussed.
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PMID:A new animal model for schizophrenia: interactions with adrenergic mechanisms. 20 65

Amphetamine (A) (9.2 mg/kg, IP), in combination with iprindole (I) (10.0 mg/kg, IP), caused long-lasting dopamine (DA) depletions in striatum (-49%, 4 weeks) but not in nucleus accumbens following one A/I injection. Striatal DA had recovered by 4 months. DA receptors (DAr) were up-regulated: 1) behavioral responses to a DA receptor agonist (apomorphine) were significantly elevated. These included apomorphine-induced locomotor activity (+103% and +160%, on weeks 3 and 10) and apomorphine-induced stereotypy (day 10). 2) Bmax for [3H]spiroperidol binding to striatal D2 DAr (12 weeks) increased (+53%, week 12). Injection of the DAr neuromodulator cyclo(leucyl-glycyl) (8 mg/kg/day x 4 days, SC) reversed the Bmax increase. Thus toxicity (DA depletion) following high-dose amphetamine appears to induce compensatory changes in DAr. This DAr upregulation may explain the lack of abnormal movements despite enduring DA depletion. Additionally, the A/I paradigm as an animal model of long-lasting DAr up-regulation, could be used to screen neuromodulatory agents, like CLG, that might treat disorders (e.g., tardive dyskinesia and schizophrenia) thought to involve up-regulated DAr.
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PMID:Long-lasting dopamine receptor up-regulation in amphetamine-treated rats following amphetamine neurotoxicity. 181 75

Amphetamine is known to elicit stereotyped behavior in various species. For a long time, this effect was considered to be an animal model for the positive symptoms of schizophrenia. In addition, amphetamine is known to induce a strong social isolation in socially living monkeys. Both on symptomatologic and pharmacologic grounds, this amphetamine-induced social isolation has been suggested to represent an animal model for the negative symptoms of schizophrenia. To date no effective treatment has been found for these negative symptoms. We now report that the selective D1 dopamine antagonist SCH 23390 is very effective in antagonizing both the stereotyped behavior and the social isolation in Java monkeys induced by amphetamine. Moreover, SCH 23390 is able to reinstate normal behavior in these animals. These results may have important consequences for our understanding of the functional significance of the D1 receptor as well as for the clinical treatment of the positive and negative symptoms of schizophrenia.
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PMID:Are antagonists of dopamine D1 receptors drugs that attenuate both positive and negative symptoms of schizophrenia? A pilot study in Java monkeys. 257 39

Changes in regional cerebral blood flow and behavioral and physiological indices were monitored after intravenous administration of d-amphetamine sulfate and placebo in groups of patients with schizophrenia and normal volunteers. Amphetamine administration was associated with decreased anxiety, emotional withdrawal, depressed mood, blunted affect and increased excitement in the patients. Subjects who received amphetamine showed significant increases in systolic and diastolic blood pressure and reduction in end-tidal carbon dioxide. Post-amphetamine cerebral blood flow was decreased equally in both patients and controls. The blood flow change, however, did not show any regional variations.
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PMID:Changes in cerebral blood flow and mental state after amphetamine challenge in schizophrenic patients. 261 28

The hypothesis of two independent pathologies in schizophrenia proposed by Crow (1980) were tested. Two dimensions of the dopamine variable, namely, the behavioral response during the Amphetamine Challenge Test (ACT) and the response to neuroleptic treatment, were studied in a cohort of 19 subjects with a research diagnosis of schizophrenia (n = 18) or schizoaffective disorder (n = 1) in an acute inpatient setting. The size of the lateral ventricle was assessed by mesauring the ventricle-brain ratio (VBR) on the computerized tomographic brain scan. Patients who had greater symptom reduction with the neuroleptic treatment worsened more in their positive psychotic symptoms during the ACT. Those with larger VBRs showed less treatment responsiveness and no worsening during the ACT. The findings are supportive of Crow's hypothesis. The ACT has the potential to be an index of both Type I and Type II pathologies.
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PMID:Amphetamine challenge test, response to treatment, and lateral ventricle size in schizophrenia. 264 57

Amphetamine induced psychosis has for the past 30 years provided a useful model for the study of schizophrenia. The amphetamine model, however, has been shown to have a number of shortcomings including an inability to model the deficit symptoms of schizophrenia. PCP (phencyclidine) has been shown to be capable of inducing a schizophreniform psychosis consisting of both productive and defict symptomatology. PCP induced psychosis, therefore, may provide a useful model of schizophrenia. This paper reviews the literature concerning the PCP model of schizophrenia and provides some independent confirmation of the ability of PCP to modulate mesocortical dopaminergic activity. Since PCP appears to mediate its CNS effects via a subclass of glutamate receptors, a possible glutamate theory of schizophrenia is proposed.
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PMID:Negative schizophrenic symptomatology and the PCP (phencyclidine) model of schizophrenia. 282 Aug 54

Central mechanisms of sensory gating were assessed in Sprague-Dawley rats using an evoked potential technique similar to one that we have previously employed to show diminished sensory gating in psychotic patients. Gating mechanisms were examined using a conditioning-testing paradigm in which pairs of 74-dB clicks were delivered; the interval between the conditioning and test stimuli was 0.5 sec. A middle latency auditory evoked response (N50) recorded from the skull of unanesthetized, freely moving rats demonstrated significant suppression to the test click. Systemic administration of amphetamine (1 mg/kg, ip) significantly reduced the amount of suppression of the response to the test stimulus; haloperidol (1 mg/kg), injected after the amphetamine, returned the conditioning-testing suppression ratio toward normal values. Amphetamine also decreased the latency and amplitude of the conditioning response, an effect that was also reversed by haloperidol. Both decreased suppression of the test response and reduced amplitude and latency of the conditioning response have been observed in schizophrenia. To aid in determining the underlying mechanism of these effects, the animals were treated with two doses, given at a 1-week interval, of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine) (DSP4; 50 mg/kg, ip), an agent that selectively depletes central norepinephrine. The extent and selectivity of the depletions were confirmed by chemical analysis. Following DSP4, the effects of amphetamine on the amplitude and latency of the conditioning response were largely unchanged. However, pretreatment with DSP4 significantly attenuated the reduction in conditioning-testing suppression observed following the administration of amphetamine. The data suggest a specific role for norepinephrine in the modulation of sensory processing.
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PMID:Modulation of the gating of auditory evoked potentials by norepinephrine: pharmacological evidence obtained using a selective neurotoxin. 339 Apr 98


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