Mesolimbic and mesocortical dopamine activation induced by phencyclidine: contrasting pattern to striatal response

Deutch, Ariel Y.; Tam, See‐Ying; Freeman, Arthur; Bowers, Malcolm B.; Roth, Robert H.

doi:10.1016/0014-2999(87)90356-6

Cited by 132 publications

(75 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously discussed, some effects of acute PCP administration on subcortical dopamine transmission, especially in the nucleus accumbens, of rats have been reported (Doherty et al 1980;Deutch et al 1987; Jentsch et al 1997a). In contrast, we failed to find any effect of single-dose PCP exposure on subcortical dopamine utilization in the monkey (Jentsch et al 1997a).…”

Section: Subcortical Dopamine Dysfunctionmentioning

confidence: 88%

“…d Allen and Young (1978). e Cosgrove and Newell (1991 Deutch et al 1987;Verma and Moghaddam 1996; Jentsch et al 1997a); whereas, longterm PCP administration reduces frontal dopamine transmission (Jentsch et al 1997b,c; see below). Because hypofrontality and some cognitive deficits of schizophrenia have been associated with reduced dopamine transmission within the prefrontal cortex (Weinberger et al 1988; Daniel et al 1989Daniel et al , 1991Dolan et al 1995; reviewed in Davis et al 1991;Knable and Weinberger 1997), these findings suggest that long-term administration of NMDA receptor antagonists produces effects that are most consistent with schizophrenia.…”

Section: Do Acute and Long-term Pcp Exposure Have Similar Consequences?mentioning

confidence: 99%

“…As noted above, acute administration of noncompetitive NMDA receptor antagonists is associated with a dramatic activation of dopamine transmission in forebrain (Doherty et al 1980; Bowers and Hoffman 1984;Deutch et al 1987;Verma and Moghaddam 1996; Jentsch et al 1997a), and this effect is likely directly implicated in the cognitive dysfunction exhibited by subjects acutely treated with PCP or ketamine (Verma and Moghaddam 1996), because increased dopamine transmission in prefrontal cortex has been reported to impair spatial working memory (Murphy et al 1996a; Jentsch et al 1997d). In rodents, an acute dose of PCP seems to augment prefrontal cortical and ventral striatal dopamine transmission; whereas, the dopaminergic innervation of the dorsal striatum is relatively unaffected (Deutch et al 1987; Jentsch et al 1997a).…”

Section: Neurochemistry Cortical Dopamine Dysfunctionmentioning

confidence: 99%

“…In rodents, an acute dose of PCP seems to augment prefrontal cortical and ventral striatal dopamine transmission; whereas, the dopaminergic innervation of the dorsal striatum is relatively unaffected (Deutch et al 1987;Jentsch et al 1997a). In the monkey, we measured marked increases in frontal cortical dopamine utilization in PCP-treated monkeys, but no change was noted in any subcortical region, including the nucleus accumbens (Jentsch et al 1997a).…”

Section: Neurochemistry Cortical Dopamine Dysfunctionmentioning

confidence: 99%

“…In the monkey, we measured marked increases in frontal cortical dopamine utilization in PCP-treated monkeys, but no change was noted in any subcortical region, including the nucleus accumbens (Jentsch et al 1997a). Acute PCP administration has also been reported to activate serotonergic, glutamatergic, noradrenergic, cholinergic, and neurotensinergic transmission in rodents and monkeys (see below) (Deutch et al 1987; Jentsch et al 1997a).Previously, it was suggested that inhibition of dopamine re-uptake was directly implicated in the acute PCP-induced increases in extracellular levels of dopamine in prefrontal cortex and nucleus accumbens (McCullough and Salamone 1992;Steinpreis and Salamone 1993; Hondo et al 1994); however, several lines of data refute this hypothesis. The activation of dopamine transmission in the prefrontal cortex and nucleus accumbens induced by acute PCP administration is blocked by such agents as (Ϯ)HA966, prazosin, and clonidine (Mathe et al 1996; Jentsch et al 1997a Jentsch et al , 1998b, which modulate the firing patterns of dopaminergic neurons within the ventral mesencephalon (Shepard et al 1996; Svensson 1989, 1993) and by intraprefrontal cortical administration of tetrodotoxin (Nishijima et al 1996).…”

mentioning

confidence: 99%

See 4 more Smart Citations

The Neuropsychopharmacology of Phencyclidine From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia

Jentsch

Roth²

1999

Neuropsychopharmacology

1,202

772

View full text Add to dashboard Cite

Administration of noncompetitive NMDA ր glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology, findings that have contributed to a hypoglutamatergic hypothesis of schizophrenia. Moreover, a history of experimental investigations of the effects of these drugs in animalsBiological psychiatric research has seen the development of many putative animal models of schizophrenia. The etiological bases of these models have varied widely from the administration of purportedly psychotomimetic drugs (Snyder 1988; Javitt and Zukin 1991; Jentsch et al. 1998a), to perinatal insults (Lipska et al. 1993;El-Khodor and Boksa 1997;Moore and Grace 1997; Bertolino et al. 1997), to chronic social isolation or stress (Jones et al. 1990), and beyond. The administration of psychotomimetic drugs to humans and animals represents probably the most widely accepted and utilized class of schizophrenia models. These "pharmacological" models seem to represent methods for the induction of psychopathology in humans and aberrant (potentially related) behavior in animals.At the behavioral level, there seems to be some heterogeneity in the effects of different psychotomimetic drug classes. The psychomotor stimulants, such as amphetamine and cocaine, can clearly induce a form of 20 , NO . 3 paranoid psychosis in human subjects after high-dose or long-term administration, but evidence regarding the ability of these agents to induce "deficit" state symptoms is conflicting (Angrist and Gershon 1970;Everitt et al., 1997); moreover, there is evidence that amphetamine may actually alleviate negative and cognitive symptoms in schizophrenic patients (Angrist et al. 1982;Goldberg et al. 1991; Carter et al. 1997). Psychotomimetic indoleamines, such as lysergic acid diethylamide, can induce profound sensory hallucinations without causing any apparent deficit state in normal subjects (Geyer and Markou 1994) and without precipitating symptomatology in schizophrenic patients (Cohen et al. 1962). In contrast, the noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) ր glutamate receptor, including phencyclidine (PCP) and ketamine, seem to be capable of inducing both positive and negative symptoms of schizophrenia, including cognitive dysfunction in normal humans (Snyder 1980; Javitt and Zukin 1991;Tamminga 1998); these drugs also profoundly exacerbate both positive and negative symptoms in schizophrenic patients (Itil et al. 1967;Lahti et al. 1994;Malhotra et al. 1997a).Because of the more comprehensive psychopathology induced by PCP, many researchers have studied the effects of NMDA receptor antagonists in humans and animals to gain insights into the neurobiology of schizophrenia. In this review, the validity of NMDA receptor antagonist-induced models of schizophrenia in humans and animals are considered, and the applicability of acute versus chronic administration of PCP as a more precise model is assessed. The neurobiological substrates of the observed behavior...

show abstract

Section: Subcortical Dopamine Dysfunctionmentioning

confidence: 88%

Section: Do Acute and Long-term Pcp Exposure Have Similar Consequences?mentioning

confidence: 99%

Section: Neurochemistry Cortical Dopamine Dysfunctionmentioning

confidence: 99%

Section: Neurochemistry Cortical Dopamine Dysfunctionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The Neuropsychopharmacology of Phencyclidine From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia

Jentsch

Roth²

1999

Neuropsychopharmacology

1,202

772

View full text Add to dashboard Cite

show abstract

Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis

Nishijima

Kashiwa

Hashimoto

et al. 1996

Synapse

View full text Add to dashboard Cite

We have examined the effects of schizophrenomimetic drugs including phencyclidine (PCP) and methamphetamine (MAP) on cortical and striatal dopamine (DA) metabolism using an in vivo dialysis technique in the rat. An acute systemic injection of PCP (2.5–10 mg/kg, intraperitoneally (i.p.)) dramatically increased concentrations of DA, 3,4‐dihydroxy‐phenylacetic acid, and homovanillic acid in the dialysates from the medial frontal cortex in a dose‐dependent fashion. However, PCP (2.5–10 mg/kg, i.p.) caused a much lower augmentation of extracellular DA release, with a significant decrease in dialysate DOPAC levels in the striatum. Moreover, continuous infusion of tetrodotoxin (TTX, 10−5 M) into the prefrontal or striatal region through the microdialysis tube completely blocked the ability of PCP (10 mg/kg, i.p.) to alter the extracellular release of DA and its metabolites in the respective areas. In contrast, MAP (4.8 mg/kg, i.p.) elicited a marked and tetrodotoxin‐resistant increase in DA levels with a significant loss of DOPAC contents in the extracellular space of both the frontal cortex and the striatum. The present results clearly demonstrate the differential effects of PCP on cortical and striatal DA transmission, suggesting that PCP may facilitate DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area, whereas PCP‐induced elevation of extracellular DA in the striatum may be caused mainly by reuptake inhibition of DA liberated by basal activity of the striatal DA neurons. The regional variation in PCP‐induced DA release would be due to the combination of NMDA (N‐methyl‐D‐aspartate) receptor blocking and DA reuptake inhibition by the drug. The uniform and TTX‐resistant nature of MAP‐induced changes in brain DA metabolism may result from the direct actions of MAP at DA nerve terminals. © 1996 Wiley‐Liss, Inc.

show abstract

?-noradrenergic receptor modulation of the phencyclidine- and ?9-tetrahydrocannabinol-induced increases in dopamine utilization in rat prefrontal cortex

Jentsch¹,

Wise²,

Katz³

et al. 1998

Synapse

Self Cite

View full text Add to dashboard Cite

The noncompetitive NMDA receptor antagonist phencyclidine (PCP) and the neuronal cannabinoid receptor agonist delta9-tetrahydrocannabinol (THC) are two agents shown to have psychotomimetic properties in humans. Both drugs increase dopamine release and utilization in the prefrontal cortex, a brain region thought to be dysfunctional in schizophrenia. In the present series of studies, the effects of drugs acting at alpha-noradrenergic receptors on PCP- and THC-induced increases in prefrontal cortical and nucleus accumbens dopamine utilization in the rat were examined. Clonidine, an alpha2 noradrenergic receptor agonist, completely blocked the activation of mesoprefrontal dopamine system by THC or PCP. In addition, the alpha1 noradrenergic receptor antagonist prazosin blocked the PCP-induced increase in prefrontal cortical dopamine utilization. These data may provide new insights concerning pharmacological therapies for acute drug-induced psychoses and behavioral abnormalities in human PCP and THC abusers.

show abstract

Mesolimbic and mesocortical dopamine activation induced by phencyclidine: contrasting pattern to striatal response

Cited by 132 publications

References 44 publications

The Neuropsychopharmacology of Phencyclidine From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia

The Neuropsychopharmacology of Phencyclidine From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia

Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis

?-noradrenergic receptor modulation of the phencyclidine- and ?9-tetrahydrocannabinol-induced increases in dopamine utilization in rat prefrontal cortex

Contact Info

Product

Resources

About