Withdrawal of repeated cocaine decreases autoradlographic [3H]mazindol-labelling of dopamine transporter In rat nucleus aecumbens

Sharpe, Lawrence G.; Pilotte, Nancy S.; Mitchell, W. M.; Souza, Errol B. De

doi:10.1016/0014-2999(91)90804-y

Cited by 108 publications

(59 citation statements)

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“…That is, the same cocaine-induced adaptation in the VTA, which has presumably returned to its basal state after the withdrawal of cocaine, has a profoundly different behavioral effect because cocaine-induced adaptations in the NAc and other target regions are much longer-lasting, perhaps even permanent (Robinson and Berridge, 1993;Wolf, 1998;Vanderschuren and Kalivas, 2000). Long-lasting changes in neurotransmission in the motive circuit include D 1 receptor supersensitivity in the NAc (Xu et al, 1994), as well as decreased dopamine transporter binding sites (Sharpe et al, 1991;Pilotte et al, 1994) and mRNA after 10 d of withdrawal from chronic cocaine treatment (Xia et al, 1992). In addition, repeated amphetamine administration in the VTA resulted in an increased sensitivity of NAc medium spiny neurons to the inhibitory effects of a D 1 receptor agonist on firing rates (Hu et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

Borgland¹,

Malenka²,

Bonci³

2004

J. Neurosci.

270

266

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The initiation of the psychostimulant sensitization process depends on the mesolimbic system, which projects from the ventral tegmental area (VTA) to the nucleus accumbens. Although such initiation is primarily dependent on glutamatergic activity in VTA neurons, the exact role VTA excitatory synapses play in this process is poorly understood. Here, we examine the effects of repeated in vivo injections of cocaine on the magnitude and duration of the increase in strength at VTA excitatory synapses reported previously to be elicited by a single in vivo exposure to cocaine (Ungless et al., 2001; Saal et al., 2003). We also compare the synaptic modifications induced by cocaine with its effects on locomotor activity. Surprisingly, repeated cocaine exposure potentiated the ratio of AMPA receptor-mediated to NMDA receptor-mediated EPSCs to a similar extent and duration as a single in vivo cocaine exposure. In naive animals, the magnitude of the cocaine-induced locomotor activity after a single injection of cocaine correlated with the magnitude of the accompanying synaptic enhancement. This correlation was lost on the seventh day of repeated cocaine administration, as well as when a challenge injection was given 10 d after the cessation of repeated cocaine administration. These results suggest that the cocaine-induced synaptic plasticity at VTA excitatory synapses is transient, and its duration depends on the last exposure to cocaine. Furthermore, chronic cocaine exposure disrupts the normal, presumably adaptive relationship between synaptic enhancement in the VTA and behavior.

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Section: Discussionmentioning

confidence: 99%

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

Borgland¹,

Malenka²,

Bonci³

2004

J. Neurosci.

270

266

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“…For each ligand, an overall two-way ANOYA was conducted to (1987) [3H] AMPA (52.1 Ci/mmol)/ Maren et al (1993) [3H] mazindol (19.9 Ci/mmol)/ Sharpe et al (1991) [3H] TCP (45.4 Ci/mmol)/ Maragos et al (1991) in, which showed only regional effects. Consequently, no further analyses were conducted for ketanserin.…”

Section: Methodsmentioning

confidence: 99%

Long‐Term Changes in Brain Following Continuous Phencyclidine Administration: An Autoradiographic Study using Flunitrazepam, Ketanserin, Mazindol, Quinuclidinyl benzilate, Piperidyl‐3,4‐³H(N)‐TCP, and AMPA Receptor Ligands

Ellison

Keys

Noguchi

1999

Pharmacology & Toxicology

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Phencyclidine induces a model psychosis which can persist for prolonged periods and presents a strong drug model of schizophrenia. When given continuously for several days to rats, phencyclidine and other N-methyl-D-aspartate (NMDA) antagonists induce neural degeneration in a variety of limbic structures, including retrosplenial cortex, hippocampus, septohippocampal projections, and piriform cortex. In an attempt to further clarify the mechanisms underlying these degeneration patterns, autoradiographic studies using a variety of receptor ligands were conducted in animals 21 days after an identical dosage of the continuous phencyclidine administration employed in the previous degeneration studies. The results indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-3H(N)-TCP (TCP), f1unitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously. Quinuclidinyl benzilate and (AMPA) binding were decreased in anterior cingulate and piriform cortex, and in accumbens and striatum. Piperidyl-3,4-3H(N)-TCP binding was decreased in most hippocampal regions. Many of these long-term alterations would not have been predicted by prior studies of the neurotoxic effects of continuous phencyclidine, and these results do not suggest a unitary source for the neurotoxicity. Whereas retrosplenial cortex, the structure which degenerates earliest, showed minimal alterations, some of the most consistent, long term alterations were in structures which evidence no immediate signs of neural degeneration, such as anterior cingulate cortex and caudate nucleus, In these structures, some of the receptor changes appeared to develop gradually (they were not present immediately after cessation of drug administration), and thus were perhaps due to changed input from regions evidencing neurotoxicity. Some of these findings, particularly in anterior cingulate, may have implications for models of schizophrenia.It is well-documented that phencyclidine and related NMDA antagonists such as ketamine can induce a model psychosis when used as an anesthetic or when self-administered by drug addicts, and can exacerbate the symptoms of chronic schizophrenics (Javit & Zukin 1991;Krystal et al. 1994;Ellison 1995), The psychoses these drugs induce can mimic a variety of schizophrenic symptoms, including flattened affect, dissociative thought disorder, depersonalization, and catatonic states. These symptoms can persist for prolonged periods of up to 7 to 10 days beyond emergence from anesthesia (Allen & Young 1978;Aniline & Pitts 1982;Meltzer et al. 1972). There is also evidence of persisting memory deficits in phencyclidine addicts (Lerner & Burns 1978).NMDA antagonists such as phencyclidine, ketamine, and dizocilpine can induce neurotoxic effects in brain. Originally observed as a neuronal vacuolization in retrosplenial cortex in rats (Olney et al. 1989), it is now apparent that this neurotoxicity can be observed using a variety of meth- odologies. When NMDA a...

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“…However, there are also conflicting reports of changes in rat DAT binding site regulation as a result of chronic cocaine administration. Cocaine exposure has been reported to increase (Alburges et al, 1993;Wilson et al, 1994a;Claye et al, 1995;Hitri et al, 1996;Tella et al, 1996), decrease (Sharpe et al, 1991;Pilotte et al, 1994Pilotte et al, , 1996Wilson et al, 1994a;Boulay et al, 1996), or have no effect (Allard et al, 1990;Kula and Baldessarini, 1991;Benmansour et al, 1992;Cass et al, 1993;Wilson et al, 1994b;Kunko et al, 1997;Letchworth et al, 1997Letchworth et al, , 1999 on the density of rat DAT binding sites. Paradigm differ-ences such as drug dose, length and route of administration, time since the final drug administration, and ligand used to identify DAT may account for the variability among these studies.…”

Section: Abstract: Cocaine; Dopamine Transporter; Striatum; Nucleus mentioning

confidence: 99%

Progression of Changes in Dopamine Transporter Binding Site Density as a Result of Cocaine Self-Administration in Rhesus Monkeys

et al. 2001

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The present study examined the time course of alterations in levels of dopamine transporter (DAT) binding sites that accompany cocaine self-administration using quantitative in vitro receptor autoradiography with [ 3 H]WIN 35,428. The density of dopamine transporter binding sites in the striatum of rhesus monkeys with 5 d, 3.3 months, or 1.5 years of cocaine selfadministration experience was compared with DAT levels in cocaine-naïve control monkeys. Animals in the long-term (1.5 years) exposure group self-administered cocaine at 0.03 mg/kg per injection, whereas the initial (5 d) and chronic (3.3 months) treatment groups were each divided into lower dose (0.03 mg/kg per injection) and higher dose (0.3 mg/kg per injection) groups. Initial cocaine exposure led to moderate decreases in [ 3 H]WIN 35,428 binding sites, with significant changes in the dorsolateral caudate (Ϫ25%) and central putamen (Ϫ19%) at the lower dose. Longer exposure, in contrast, resulted in elevated levels of striatal binding sites. The increases were most pronounced in the ventral striatum at the level of the nucleus accumbens shell. At the lower dose of the chronic phase, for example, significant increases of 21-42% were measured at the caudal level of the ventral caudate, ventral putamen, olfactory tubercle, and accumbens core and shell. Systematic variation of cocaine dose and drug exposure time demonstrated the importance of these factors in determining the intensity of increased DAT levels. With self-administration of higher doses especially, increases were more intense and included dorsal portions of the striatum so that every region at the caudal level exhibited a significant increase in DAT binding sites (20-54%). The similarity of these findings to previous studies in human cocaine addicts strongly suggest that the increased density of dopamine transporters observed in studies of human drug abusers are the result of the neurobiological effects of cocaine, ruling out confounds such as polydrug abuse, preexisting differences in DAT levels, or comorbid psychiatric conditions.

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Withdrawal of repeated cocaine decreases autoradlographic [3H]mazindol-labelling of dopamine transporter In rat nucleus aecumbens

Cited by 108 publications

References 6 publications

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

Long‐Term Changes in Brain Following Continuous Phencyclidine Administration: An Autoradiographic Study using Flunitrazepam, Ketanserin, Mazindol, Quinuclidinyl benzilate, Piperidyl‐3,4‐³H(N)‐TCP, and AMPA Receptor Ligands

Progression of Changes in Dopamine Transporter Binding Site Density as a Result of Cocaine Self-Administration in Rhesus Monkeys

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Withdrawal of repeated cocaine decreases autoradlographic [3H]mazindol-labelling of dopamine transporter In rat nucleus aecumbens

Cited by 108 publications

References 6 publications

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

Acute and Chronic Cocaine-Induced Potentiation of Synaptic Strength in the Ventral Tegmental Area: Electrophysiological and Behavioral Correlates in Individual Rats

Long‐Term Changes in Brain Following Continuous Phencyclidine Administration: An Autoradiographic Study using Flunitrazepam, Ketanserin, Mazindol, Quinuclidinyl benzilate, Piperidyl‐3,4‐3H(N)‐TCP, and AMPA Receptor Ligands

Progression of Changes in Dopamine Transporter Binding Site Density as a Result of Cocaine Self-Administration in Rhesus Monkeys

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Long‐Term Changes in Brain Following Continuous Phencyclidine Administration: An Autoradiographic Study using Flunitrazepam, Ketanserin, Mazindol, Quinuclidinyl benzilate, Piperidyl‐3,4‐³H(N)‐TCP, and AMPA Receptor Ligands