Phenothiazine Effects on Psychological and Psychophysiological Dysfunction in Chronic Schizophrenics

Spohn, Herbert; Lacoursiere, Roy B.; Thompson, Karen; Coyne, Lolafaye

doi:10.1001/archpsyc.1977.01770180019001

Cited by 238 publications

(106 citation statements)

References 40 publications

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“…This highlights another important factor that might influence the evaluation of the effect of neuroleptics on CPT performance: the format of the CPT. Of the three studies that used the simple X version of the CPT (Erickson et al 1984;Orzack et al 1967;Spohn et al 1977), only one of them failed to detect significant change in performance, probably because of small sample sizes (n ϭ 11). The authors also attributed their failure to detect change in performance partly to the immature attentional mechanism of their adolescent samples (Erickson et al 1984).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, if attention deficits in schizophrenia represent stable vulnerability indicators, one would expect CPT performance to be unchanged after effective neuroleptic treatment. Orzack et al (1967) have first reported that effective neuroleptic medication leads to improvement in both CPT performance and global symptoms in schizophrenic patients, and three subsequent studies with similar longitudinal designs that measured within-subject changes have reported similar findings (Mirsky et al 1984;Nuechterlein et al 1991;Spohn et al 1977). However, four other longitudinal studies have failed to detect any change in CPT performance in schizophrenic patients in response to neuroleptics (Cornblatt et al 1997;Epstein et al 1996;Erickson et al 1984;Finkelstein et al 1997).…”

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confidence: 97%

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Effects of Atypical Neuroleptics on Sustained Attention Deficits in Schizophrenia A Trial of Risperidone Versus Haloperidol

Liu

Chen

Chang

et al. 2000

Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Effects of Atypical Neuroleptics on Sustained Attention Deficits in Schizophrenia A Trial of Risperidone Versus Haloperidol

Liu

Chen

Chang

et al. 2000

Neuropsychopharmacology

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Section: Latent Inhibition (Li) Is a Behavioral Phenomenon Whereby Rementioning

confidence: 99%

“…Importantly, AMPH-induced disruptions in LI can also be reversed by neuroleptic treatment (Warburton et al 1994;Moran et al 1996;Weiner et al 1996b). Clinical studies have suggested that neuroleptics have similar enhancement effects on LI in humans (Williams et al 1996 but see Williams et al 1998) in addition to improving performance in other tests of selective attention in which schizophrenics show deficits (Spohn et al 1977;Braff and Sacuzzo 1982).We recently observed that pretreatment with escalating doses of AMPH disrupts LI for up to at least two weeks after the last AMPH injection in rats tested in a 2-way active avoidance paradigm . We hypothesize that the disruptive effects of AMPH withdrawal on LI may mimic symptoms of cognitive disorganization similar to those found in schizophrenia.…”

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confidence: 99%

Clozapine and Haloperidol Reinstate Latent Inhibition Following its Disruption during Amphetamine Withdrawal

Russig

Murphy

Feldon

2002

Neuropsychopharmacology

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Latent inhibition (LI) is a behavioral phenomenon whereby repeated exposure to a non-reinforced stimulus retards subsequent conditioning to that stimulus. Deficits in LI may reflect an inability to ignore irrelevant stimuli and are studied as a model of the cognitive/attentional abnormalities found in schizophrenia. We recently determined that pretreatment with escalating doses of the indirect dopamine agonist amphetamine (AMPH; 3 daily injections ip, 1-5 mg/kg, over 6 days) disrupts LI in ratsAmphetamine (AMPH) administration can induce symptoms of psychosis in humans. This outcome is most frequently observed following a chronic high-dose escalating pattern of stimulant abuse (Davis and Schlemmer 1980;Angrist 1994). Given that stimulant-induced psychosis resembles the psychosis observed in patients with idiopathic schizophrenia (Ellinwood 1967;Snyder 1973;Brady et al. 1991), it has been suggested that similar neural adaptations could be responsible for the development of these two phenomena. In experimental animals, repeated exposure to AMPH induces behavioral sensitization, a phenomenon that is indicated by a progressive augmentation of behaviors (e.g. locomotion, stereotypies) to subsequent drug challenges and can persist even after prolonged periods of abstinence (Robinson and Becker 1986). Consequently, it has been proposed that studies of the neural bases of behavioral sensitization in animals may yield insights into the neuropathology of schizophrenia (Kokkinidis and Anismann 1980;Robinson and Becker 1986;Liebermann et al. 1990). 26 , NO . 6 In contrast to the sensitizing effects of repeated psychostimulant challenges on behavior, several reports indicate that withdrawal from repeated stimulant administration induces a state of dysphoria, characterized by symptoms that include anhedonia, anxiety and lethargy. Although such symptoms typically persist for only the first few days of abstinence, these findings have prompted the study of acute psychostimulant withdrawal as an animal model of depression (Leith and Barrett 1976;Kokkinidis et al. , 1986Geyer and Markou 1995;Barr and Phillips 1999;Lin et al. 1999). Given the proposed links between behavioral sensitization to AMPH in rats and psychosis in humans, and evidence of cross-sensitization between AMPH and stress (Antelman et al. 1980), we recently attempted to further characterize how animals in withdrawal from AMPH might demonstrate altered responses to environmental stimulation. We hypothesized that AMPH-withdrawn animals may also exhibit behaviors consistent with recognized models of schizophrenia.Many investigators studying animal models of cognitive deficits in schizophrenia have evaluated the behavioral phenomenon of latent inhibition (LI). LI refers to the process whereby repeated exposure to a conditioned stimulus (CS) without consequence impedes the formation of subsequent associations between the CS (e. g. a tone) and a relevant unconditioned stimulus (UCS; e. g. a footshock; Lubow 1973). Reductions in LI have been reported in acute schizop...

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“…Antipsychotic drugs (APDs) are dopamine (DA) receptor antagonists (Carlsson and Lindqvist, 1963) and their efficacy is highly correlated with their ability to block DA receptors (Creese et al, 1976;Seeman et al, 1976;Kebabian and Calne, 1979). Nonetheless, although APDs will block DA receptors within minutes following their administration (Rupniak et al, 1983;Sedvall et al, 1986), these drugs must be administered for weeks before achieving maximal therapeutic efficacy and before the Parkinsonian motor side effects are manifest (Spohn et al, 1977;Cotes et al, 1978;Davis and Garver, 1978;Johnstone et al, 1978;Cooper et al, 1990). The time-dependent effects of classic APDs in humans have been temporally correlated with the development of depolarization block of DA cell firing in rats, in which repeated haloperidol treatment causes a cessation of spontaneous spike discharge in the majority of mesencephalic DA neurons in the substantia nigra (SN, A9) and the ventral tegmental area (VTA, AlO) (Bunney and Grace, 1978;Chiodo and Bunney, 1983;White and Wang, 1983;Grace and Bunney, 1986).…”

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confidence: 99%

Repeated treatment with haloperidol and clozapine exerts differential effects on dye coupling between neurons in subregions of striatum and nucleus accumbens

Onn

Grace

1995

J. Neurosci.

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The delayed onset of action of antipsychotic drugs (APDs) during the treatment of schizophrenia has been hypothesized to temporally correlate with the induction of depolarization block in rat mesencephalic dopamine (DA) cell groups. Nevertheless, it is unknown whether these drugs also exert a delayed action on the dopaminoceptive postsynaptic target cells in the striatal complex. Using in vivo intracellular recording and dye labeling techniques, the effects of APDs on dye coupling were examined in subregions of the striatal complex defined by double staining for calbindin immunoreactivity. Rats treated repeatedly with APDs were found to exhibit a 66–71% higher incidence of coupling that occurred in a drug- and a region-specific manner, that is, both drug treatments increased dye coupling in the limbic-associated accumbens shell region whereas only haloperidol increased dye coupling in the motor-related striatal matrix and accumbens core regions. In addition, cells located in regions in which dye coupling was altered also showed significantly higher input resistance. These changes were not observed in response to DA receptor blockade by acute drug administration or when haloperidol was administered for a period sufficient to induce DA receptor supersensitivity but not DA cell depolarization block (i.e., 2 weeks). Therefore, alteration in dye coupling appears to be correlated temporally with the induction of DA cell depolarization block. The finding that both APDs exert a common action on neurons in the accumbens shell region is consistent with its identification as the site of therapeutic drug actions, whereas the capacity of haloperidol to also affect cells in the motor-related matrix and core regions correlates with its high propensity to induce extrapyramidal side effects.

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Phenothiazine Effects on Psychological and Psychophysiological Dysfunction in Chronic Schizophrenics

Cited by 238 publications

References 40 publications

Effects of Atypical Neuroleptics on Sustained Attention Deficits in Schizophrenia A Trial of Risperidone Versus Haloperidol

Effects of Atypical Neuroleptics on Sustained Attention Deficits in Schizophrenia A Trial of Risperidone Versus Haloperidol

Clozapine and Haloperidol Reinstate Latent Inhibition Following its Disruption during Amphetamine Withdrawal

Repeated treatment with haloperidol and clozapine exerts differential effects on dye coupling between neurons in subregions of striatum and nucleus accumbens

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