Effects of d-amphetamine and phencyclidine on behavior and extracellular concentrations of neurotensin and dopamine in the ventral striatum and the medial prefrontal cortex of the rat

Hertel, P.; Mathé, Jan M.; Nomikos, George G.; Iurlo, M.; Mathé, Aleksander A.; Svensson, Torgny H.

doi:10.1016/0166-4328(96)00138-6

Cited by 117 publications

(64 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using a match variant of the task employed here, Chudasama and Robbins (2004a) also provided evidence for an important neuromodulatory influence of dopamine D1 agonists in working memory performance. PCP also evokes the release of dopamine into the prefrontal cortex (Bowers and Morton, 1994;Deutch et al, 1987;Hertel et al, 1995), and clonidine is effective at suppressing dopaminergic hyperactivity evoked by PCP (Jentsch et al, 1998). Taken together, these neurochemical and behavioral data indicate that a role for dopamine in the current results must also be considered.…”

Section: Discussionmentioning

confidence: 65%

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

Marrs

Kuperman

Avedian

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists, such as phencyclidine (PCP), induce behavioral abnormalities (locomotor hyperactivity, sensorimotor gating deficits, impairments of cognition) in animals that are thought to model aspects of schizophrenia. The administration of PCP increases noradrenaline transmission in the rat prefrontal cortex, a brain structure required for normal cognitive processes. Noradrenaline, in turn, works through a set of receptors that have themselves been implicated directly in NMDA antagonist-induced deficits; we recently reported that the alpha-2 agonist, clonidine, is effective at preventing PCP-induced deficits of working memory and visual attention in rats. Here, we further investigated the role for alpha-2 adrenoreceptors in the effects of PCP on spatial working memory performance. The alpha-2 agonist clonidine (0.001-0.01 mg/kg, subcutaneously (s.c.)) produced a significant amelioration of PCP-induced working memory deficits; the effects of PCP (1.0 mg/kg, s.c.), but not clonidine, were reduced in noradrenaline-depleted rats. In addition, the alpha-2A-preferring agonist guanfacine (0.05-1.0 mg/kg, s.c.) dose-dependently prevented the deficits of spatial working memory performance produced by PCP. Although the highly selective alpha-2 receptor antagonist, atipamezole (ATI), failed to affect spatial working memory on its own, at the doses studied (0.1-0.5 mg/kg, s.c.), it dramatically enhanced the working memory deficit produced by PCP. These data indicate that alpha-2 adrenoreceptors tonically inhibit PCP-induced deficits of spatial working memory, suggesting an important role for these receptors in cognitive deficits associated with NMDA receptor hypofunction.

show abstract

Section: Discussionmentioning

confidence: 65%

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

Marrs

Kuperman

Avedian

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…In a previous experiment, similar administration of d-amphetamine or PCP increased extracellular concentrations of both NT-LI and DA in the VSTR and medial prefrontal cortex, although the effect of d-amphetamine on NT-LI in the VSTR did not attain statistical significance (Hertel et al 1996). This may be due to the differences in experimental procedures, including use of different NT antibodies in RIA.…”

Section: Discussionmentioning

confidence: 76%

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Gruber

Nomikos

Mathé

2002

Neuropsychopharmacology

View full text Add to dashboard Cite

Neurotensin (NT) may play a role in the pathophysiology of schizophrenia and in the mechanism of action of antipsychotic drugs. Here we studied the effects of a 30-day regimen of haloperidol (1.15 mg/100 g food) and risperidone (1.15 and 2.3 mg/100 g food) on NT-like immunoreactivity (-LI) levels in brain tissue and NT-LI efflux in the ventral striatum (VSTR) of the rat. Haloperidol, but not risperidone, increased NT-LI levels in the striatum. In the occipital cortex, risperidone, but not haloperidol, decreased levels of NT-LI. In the hippocampus and the frontal cortex both haloperidol and risperidone (the higher dose) increased NT-LI levels. In the VSTR, haloperidol and risperidone (the higher dose) decreased NT-LI efflux and abolished the stimulatory effect of d-amphetamine (1.5 mg/kg, s.c.). Thus, changes in NT occur in response toNeurotensin (NT) is a 13-amino acid peptide originally isolated from hypothalamus (Carraway and Leeman 1973). Several anatomical, behavioral and pharmacological studies have demonstrated an interaction between NT and dopamine (DA) in the central nervous system (CNS). For example, high levels of NT and its binding sites have been found in both the cell body regions, i.e. the substantia nigra pars compacta (SN) and the ventral tegmental area (VTA), as well as the major projection areas of the ascending dopaminergic pathways, i.e. the striatum and the nucleus accumbens (Kasckow and Nemeroff 1991;Lambert et al. 1995; Quirion 1983). Within both the VTA and the SN, NT immunoreactive fibers are found in close proximity to DA cell bodies (Hökfelt et al. 1984); within the VTA, NT is colocalized with DA (Hökfelt et al. 1984;Kalivas 1993), while in the striatal complex, the majority of the NT binding sites in rat are located on DA terminals (Cadet et al. 1991). There exists substantial pharmacological evidence showing that NT is involved in the regulation of DA neurotransmission. For example, local perfusion with NT dose-dependently increases striatal extracellular DA levels without affecting DA metabolite levels and modifies the inhibitory effects of DA-D 1 and DA-D 2 receptor agonists on striatal DA release (Fuxe et al. 1992). In contrast to the striatum, in the nucleus accumbens direct infu- NO . 5 sion of NT does not affect extracellular DA levels, but increases extracellular levels of the DA metabolite homovanillic acid (Chapman et al. 1992). Microinjection of NT into the VTA, produces a dose-dependent in vivo DA release in the nucleus accumbens and also causes a dose-dependent circling behavior (Steinberg et al. 1995). Moreover, blockade of NT receptors by the NT receptor antagonist SR 48692 decreases basal extracellular levels of DA and its metabolites in the nucleus accumbens, suggesting that NT modulates the mesolimbic DA system (Azzi et al. 1998). Neurotensin has also been shown to mimic the effects of neuroleptic drugs in behavioral models of antipsychotic drug action. Thus, centrally injected NT antagonizes psychostimulant-induced locomotor hyperactivity (Ervin et al. 1981;Joli...

show abstract

“…The effects of PCP on brain dopamine systems has received particular attention (Meltzer et al 1980;Bowers and Hoffman 1984;Deutch et al 1987;Hertel et al 1996;Jentsch et al 1997a) since alterations in dopaminergic systems have been hypothesized in schizophrenia (reviewed in Davis et al 1991;Deutch 1992 Recent work has shown that long-term administration of PCP causes enduring cognitive dysfunction and cortical dopamine deficits in rats and monkeys (Jentsch et al 1997b,c). These data correspond to reports of cognitive disturbances in schizophrenic subjects (Fey 1951;Goldman-Rakic 1991;Park and Holzman 1992), and recent in vivo imaging studies of the schizophrenic brain have revealed a failure of activation of frontal cortex during cognitive performance (termed "hypofrontality" by Weinberger and Berman 1996), effects that may be mediated by dopaminergic dysfunction Daniel et al 1989 Daniel et al , 1991Dolan et al 1995).…”

Section: Previous Studies Have Shown That Repeated Exposures To Phencmentioning

confidence: 99%

mentioning

confidence: 99%

Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

Jentsch

Taylor

Roth

1998

Neuropsychopharmacology

147

View full text Add to dashboard Cite

Previous studies have shown that repeated exposures to phencyclidine (PCP) induces prefrontal cortical dopaminergic and cognitive deficits in rats and (Javitt and Zukin 1991); that is, administration of PCP or its congeners ketamine or dizocilpine can induce schizophrenic-like symptomatology in people (Luby et al. 1959;Krystal et al. 1994; Bunney et al. 1994) and precipitate psychosis in schizophrenics (Ital et al. 1967;Lahti et al. 1994). These compounds can stimulate both positive and negative symptoms of schizophrenia (Javitt and Zukin), including cognitive dysfunction (Cosgrove and Newell 1991). As such, PCP administration has been suggested to represent a drug-induced model of schizophrenia (Javitt and Zukin;Steinpreis 1996).The ability of PCP to simulate the symptomatology of schizophrenia in humans has led to the proposal that the behavioral pathologies evident in schizophrenia and PCP-exposed humans are caused by dysfunction of common neural substrates (Luby et al. 1959;Javitt and Zukin 1991). The effects of PCP on brain dopamine systems has received particular attention (Meltzer et al. 1980;Bowers and Hoffman 1984;Deutch et al. 1987;Hertel et al. 1996;Jentsch et al. 1997a) since alterations in dopaminergic systems have been hypothesized in schizophrenia (reviewed in Davis et al. 1991;Deutch 1992 Recent work has shown that long-term administration of PCP causes enduring cognitive dysfunction and cortical dopamine deficits in rats and monkeys (Jentsch et al. 1997b,c). These data correspond to reports of cognitive disturbances in schizophrenic subjects (Fey 1951;Goldman-Rakic 1991;Park and Holzman 1992), and recent in vivo imaging studies of the schizophrenic brain have revealed a failure of activation of frontal cortex during cognitive performance (termed "hypofrontality" by Weinberger and Berman 1996), effects that may be mediated by dopaminergic dysfunction Daniel et al. 1989 Daniel et al. , 1991Dolan et al. 1995). These data are also consistent with studies in nonhuman primates that have revealed that lesions of the prefrontal cortical dopamine innervation lead to working memory impairments (Brozoski et al. 1979), a cognitive process closely associated with this brain region (Goldman-Rakic 1987).Moreover, prefrontal cortical dopaminergic deficiencies may result in enhancement of activity of subcortical dopamine systems. Destruction of prefrontal cortical dopamine terminals has been shown to augment the response of the mesolimbic dopamine systems to stress ), amphetamine sensitization (Banks and Gratton 1994), high K ϩ -stimulation (Roberts et al. 1994), or haloperidol administration (Rosin et al. 1994). These data have supported an emerging neurochemical hypothesis of schizophrenia: cortical dopaminergic hypoactivity and subcortical dopaminergic hyperactivity (Robbins 1990;Grace 1991;Deutch 1992). Recent in vivo studies of the schizophrenic brain have revealed evidence for the subcortical component of this hypothesis; heightened responsivity to the dopamine-releasing properties of amphetamine ha...

show abstract

Effects of d-amphetamine and phencyclidine on behavior and extracellular concentrations of neurotensin and dopamine in the ventral striatum and the medial prefrontal cortex of the rat

Cited by 117 publications

References 66 publications

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

Effects of Haloperidol and Risperidone on Neurotensin Levels in Brain Regions and Neurotensin Efflux in the Ventral Striatum of the Rat

Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

Contact Info

Product

Resources

About