Basal extracellular dopamine in the nucleus accumbens during amphetamine withdrawal: a ‘no net flux’ microdialysis study

Crippens, Donita; Camp, Dianne M.; Robinson, Donita L.

doi:10.1016/0304-3940(93)90878-o

Cited by 39 publications

(34 citation statements)

References 14 publications

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“…There is evidence that the effects of antipsychotic drugs on LI are mediated in the nucleus accumbens (Gray et al 1997); furthermore, reports of reduced DA function in the nucleus accumbens during COC and AMPH withdrawal (Parsons et al 1991;Rossetti et al 1992;Weiss et al 1992Weiss et al , 1997Kuhar and Pilotte 1996) are consistent with the idea that enhanced LI reflects DA antagonism in mesolimbic targets during pre-exposure and/or avoidance testing. Nevertheless, reductions in nucleus accumbens DA during psychostimulant withdrawal are not reported by all laboratories and may be dependent on schedules of drug administration or procedural details (Crippens et al 1993;Crippens and Robinson 1994); in particular, it is very possible that the schedule of low-dose AMPH employed in this study would not have been sufficient to reduce accumbens DA during withdrawal. Finally, in an earlier study in which COC was administered subsequent to CS pre-exposure and CS-UCS conditioning, we also observed enhanced LI of conditioned freezing behavior during COC withdrawal (Murphy et al 2001).…”

Section: Discussionmentioning

confidence: 87%

Effects of psychostimulant withdrawal on latent inhibition of conditioned active avoidance and prepulse inhibition of the acoustic startle response

2001

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Rationale: Chronic intermittent administration of amphetamine and cocaine can precipitate psychotic episodes in humans and produce persistent behavioral changes (i.e. increased locomotion, stereotypy) in the rat. The psychostimulant sensitization model of psychosis holds that the repeated administration of drugs such as amphetamine and cocaine induces long-lasting neuroadaptations and behavioral outcomes in animals that parallel aspects of the schizophrenic condition. Objectives: In the present study, we attempted to validate this model further by examining the effects of short-term withdrawal from repeated administration of cocaine and amphetamine on performance in two animal behavioral models of cognitive deficits found in schizophrenia: latent inhibition and prepulse inhibition. Reductions in both of these behavioral phenomena have been reported in schizophrenic patients and in acutely amphetamine-treated rats. Methods: Animals were tested after 4 days of withdrawal from 5 days of daily systemic 20 mg/kg cocaine or 1.5 mg/kg amphetamine injections for either latent inhibition of two-way active avoidance acquisition or prepulse inhibition of an acoustic startle response. Results: Our results indicate that, rather than reducing the expression of these behaviors, withdrawal from either cocaine or amphetamine enhanced the expression of latent inhibition of the active avoidance response while having no effect on prepulse inhibition of acoustic startle. Conclusions: These data indicate that although the sensitized response to amphetamine and cocaine administration may model some aspects of schizophrenic psychosis, behaviors exhibited by sensitized animals in the absence of an acute drug challenge are not consistent with models of the positive symptoms of schizophrenia.

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Section: Discussionmentioning

confidence: 87%

Effects of psychostimulant withdrawal on latent inhibition of conditioned active avoidance and prepulse inhibition of the acoustic startle response

2001

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“…Specifically, an attenuation of LI has been linked to increased DA activity in the nucleus accumbens (Solomon and Staton 1982;Gray et al 1997). In contrast, previous reports have indicated that AMPH withdrawal is associated with either a reduction or no change in basal DA levels (Rossetti et al 1992;Segal and Kuczenski 1992;Crippens et al 1993;Paulson and Robinson 1995;Weiss et al 1997). Similarly, studies from our lab using in vivo microdialysis have indicated unchanged basal levels of DA in both the core and shell subregions of the nucleus accumbens on day 4 of withdrawal from the escalating dose schedule of AMPH used in this study (Pezze et al In press).…”

Section: Discussionmentioning

confidence: 90%

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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“…Increased DA release in the nucleus accumbens after an AMPH challenge has been repeatedly found in sensitized rats (Robinson and Becker 1986; but see Segal and Kuczenski 1992) and numerous studies have shown that both LI and PPI are disrupted by DA agonists (Swerdlow et al 1992;Weiner and Feldon 1997;Geyer et al 2001). However, basal levels of nucleus accumbens DA are reportedly reduced or unchanged during AMPH withdrawal (Rossetti et al 1992;Segal and Kuczenski 1992;Crippens et al 1993). Our laboratory has in fact shown that rats withdrawn from the AMPH schedule used in the present study showed no differences in basal DA levels, but decreased DA efflux in the shell, and increased DA efflux in the core of the nucleus accumbens during the expression of a conditioned fear response (Pezze et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Prepulse inhibition during withdrawal from an escalating dosage schedule of amphetamine

2003

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Rationale: Psychomotor stimulants can induce psychotic states in humans that closely resemble those observed in patients with idiopathic schizophrenia. Attentional and sensorimotor gating impairments are observed in schizophrenic patients using the latent inhibition (LI) and prepulse inhibition (PPI) behavioral assays, respectively. Our previous studies demonstrated that after 4 days of withdrawal from a period of amphetamine (AMPH) administration, animals exhibited disrupted LI but normal PPI. Objective: The aim of the present study was to test PPI in AMPH-withdrawn rats under experimental conditions similar to those used to best demonstrate locomotor sensitization following AMPH withdrawal. Methods: We examined the effects on PPI of (1) pairing drug injections with PPI test-associated cues, (2) administration of a low-dose dopamine agonist challenge and (3) testing following longer withdrawal periods (23, 30, 60 days). Results: Although none of these conditions revealed a disruption of PPI in AMPHwithdrawn rats, we did observe that the acoustic startle response was reduced during a restricted time period following AMPH withdrawal. Similar to our previous findings, AMPH-withdrawn animals showed disrupted LI on day 16 of withdrawal and locomotor sensitization to a challenge injection of AMPH after 62 days of withdrawal. Conclusion: We conclude that the effects of repeated AMPH on PPI are not modulated by the same experimental parameters known to be important for eliciting locomotor sensitization and that withdrawal from the schedule of AMPH administration used in this study models only specific cognitive dysfunctions linked to schizophrenic symptoms, since LI was disrupted but PPI was not affected.

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Basal extracellular dopamine in the nucleus accumbens during amphetamine withdrawal: a ‘no net flux’ microdialysis study

Cited by 39 publications

References 14 publications

Effects of psychostimulant withdrawal on latent inhibition of conditioned active avoidance and prepulse inhibition of the acoustic startle response

Effects of psychostimulant withdrawal on latent inhibition of conditioned active avoidance and prepulse inhibition of the acoustic startle response

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

Prepulse inhibition during withdrawal from an escalating dosage schedule of amphetamine

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