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Items: 9

1.
Neurotoxicol Teratol. 2018 Jan - Feb;65:42-50. doi: 10.1016/j.ntt.2017.12.010. Epub 2017 Dec 29.

Abstinence following toluene exposure increases anxiety-like behavior in mice.

Author information

1
Department of Psychology, Wayne State University, Detroit, MI, USA. Electronic address: scott.bowen@wayne.edu.
2
Department of Psychology, Wayne State University, Detroit, MI, USA; Department of Obstetrics & Gynecology, Wayne State University, Detroit, MI, USA; Merrill Palmer Skillman Institute for Child & Family Development, Wayne State University, Detroit, MI, USA.
3
Department of Psychology, Wayne State University, Detroit, MI, USA.

Abstract

The intentional misuse of volatile solvents like toluene is a persistent public health concern. Limited clinical data suggest that chronic inhalant abusers may experience signs of withdrawal, including anxiety. Behavioral withdrawal from toluene has not been examined in a preclinical model. In the current study, young adult male Swiss Webster mice were exposed to either 5000-ppm toluene vapor or air (0ppm) for 30min or 24h. Mice were tested in a battery of four behavioral tasks reflective of anxiety either immediately (0h), 24h, or 72h after the toluene exposure. Mice exposed briefly (30min) to toluene showed decreases in anxiety-like behaviors, whereas mice abstinent from toluene for 24h after a prolonged (24-h) exposure, displayed increases in anxiety-like behaviors. These increases in anxiety-like behavior were not observed 72h post toluene. However, a brief re-exposure to toluene (30min at 5000ppm) immediately before testing 24h after the prolonged exposure ameliorated behavioral differences on the plus maze task. These results of 1) decreased anxiety-like behavior immediately following acute toluene, and 2) the contrasting increase in anxiety-like behavior during abstinence from a prolonged toluene exposure, and 3) the amelioration of increases in an anxiety-like behavior following toluene re-exposure, are consistent with an interpretation of withdrawal from the single 24-hr toluene exposure. These findings support clinical reports of increased anxiety during abstinence following periods of toluene use/abuse. The results also imply that experiencing anxiety during withdrawal from toluene may contribute to the persistent use of inhalants and may be relevant to clinical treatment of inhalant abuse/addiction.

KEYWORDS:

Anxiety; Mice; Organic solvents (toluene); Withdrawal

2.
Neurosci Lett. 2017 Apr 24;647:67-71. doi: 10.1016/j.neulet.2017.03.004. Epub 2017 Mar 10.

Toluene's effects on activity and extracellular dopamine in the mouse are altered by GABAA antagonism.

Author information

1
Department of Psychology, Wayne State University, 5057 Woodward Ave, Detroit, MI, 48202, USA. Electronic address: sean.callan@wayne.edu.
2
Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI, 48202, USA.
3
Department of Psychology, Wayne State University, 5057 Woodward Ave, Detroit, MI, 48202, USA. Electronic address: scott.bowen@wayne.edu.

Abstract

The abuse of inhalants like toluene continues to be widespread around the world, especially among children and teenagers. Despite its frequency of misuse, the dynamics between dopamine (DA) and gamma-aminobutyric acid (GABA) in response to toluene exposure remains unclear. To further decipher toluene's actions, we used a dynamic exposure system in combination with microdialysis to examine in vivo the effects of acutely inhaled toluene on DA release within the mouse caudate putamen (CPu). Results show that toluene inhalation produced increases in DA levels and locomotor activity. In mice that were pretreated with the GABAA antagonist, bicuculline, there was no change in the locomotor response during toluene but activity was potentiated following toluene exposure. Bicuculline pretreatment increased extracellular DA levels during toluene exposure, suggesting that DA and GABA-releasing neuron interaction may play a role in the rewarding properties of toluene.

KEYWORDS:

Caudate putamen; Dopamine; Microdialysis; Mouse; Toluene

PMID:
28288863
DOI:
10.1016/j.neulet.2017.03.004
[Indexed for MEDLINE]
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3.
Radiother Oncol. 2016 Mar;118(3):579-80. doi: 10.1016/j.radonc.2016.01.010. Epub 2016 Feb 1.

Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).

Author information

1
Department of Radiation Oncology, William Beaumont Hospital, 3811 W. Thirteen Mile Rd, 105-RI, Royal Oak, MI 48073, USA. Electronic address: brian.marples@beaumont.edu.
2
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
3
Department of Psychology, Wayne State University, Detroit, USA.
4
Beaumont BioBank and Erb Family Core Molecular Laboratories, William Beaumont Hospital, USA.
5
Beaumont Neurosurgery, William Beaumont Hospital and Michigan Head and Spine Institute, USA.
6
Division of Geriatric Medicine, William Beaumont Hospital and Department of Internal Medicine, Oakland University-William Beaumont School of Medicine, Detroit, USA.
PMID:
26838263
DOI:
10.1016/j.radonc.2016.01.010
[Indexed for MEDLINE]
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4.
Radiother Oncol. 2016 Jan;118(1):43-51. doi: 10.1016/j.radonc.2015.10.019. Epub 2015 Nov 23.

Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).

Author information

1
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA. Electronic address: BRIAN.MARPLES@BEAUMONT.EDU.
2
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA.
3
Department of Psychology, Wayne State University, Detroit, USA.
4
Beaumont BioBank and Erb Family Core Molecular Laboratories, William Beaumont Hospital, Royal Oak, USA.
5
Beaumont Neurosurgery, William Beaumont Hospital and Michigan Head and Spine Institute, Royal Oak, USA.
6
Division of Geriatric Medicine, William Beaumont Hospital and Department of Internal Medicine, Oakland University-William Beaumont School of Medicine, Royal Oak, USA.

Abstract

BACKGROUND AND PURPOSE:

To investigate if cranial X-irradiation reduces amyloid-β (Aβ) plaques and influences cognitive function in a transgenic mouse model of AD.

METHODS AND MATERIALS:

B6.Cg-Tg (APPswePSEN1dE9)85Dbo/J AD-prone mice were given cranial X-irradiation. The number of Aβ plaques, along with expression of AD specific genes (84 genes: Mouse Alzheimer's Disease RT(2) Profiler), radiation-associated cytokines (Milliplex MAP Mouse Cytokine Chemokine Immunoassay) and immunohistochemistry (IL10, IL-1β, Iba1 CD45) was assessed. Behavioral testing was performed to relate changes in Aβ burden to cognitive function using a Morris water-maze task.

RESULTS:

Single X-ray doses reduced the number (p=0.002) and size (p=0.01) of Aβ plaques. Low-dose fractionation produced greater 50.6% (1 Gy × 10), 72% (2 Gy × 5) and 78% (2 Gy × 10) reductions. Irradiation was associated with gene (Pkp4, 1.5-fold, p=0.004) and proteomic (MIP-2, 8-fold, p=0.0024) changes at 24-48 h. Microglia increased at 4 weeks post-irradiation (p=0.001). The reduction in Aβ burden (2 Gy × 5) was associated with cognitive improvement (p=0.012).

CONCLUSION:

This is the first report that a clinically relevant course of external beam irradiation (2 Gy × 5) produces a significant reduction in AD-associated amyloid-β plaques with a subsequent improvement in cognitive function. However, longer-term studies are needed to define the precise underlying mechanism and longevity of this response.

KEYWORDS:

Amyloid-β; Murine model; Plaque clearance; Radiation

PMID:
26615717
DOI:
10.1016/j.radonc.2015.10.019
[Indexed for MEDLINE]
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5.
Neuroscience. 2017 Feb 7;342:180-187. doi: 10.1016/j.neuroscience.2015.08.050. Epub 2015 Aug 28.

Prenatal toluene exposure impairs performance in the Morris Water Maze in adolescent rats.

Author information

1
Department of Psychology, Wayne State University, Detroit, MI, United States; Behavioral Pharmacology and Toxicology Laboratory, Wayne State University, Detroit, MI, United States.
2
Department of Psychology, Wayne State University, Detroit, MI, United States; Department of Obstetrics & Gynecology, Wayne State University, Detroit, MI, United States; Merrill Palmer Skillman Institute for Child and Family Development, Wayne State University, Detroit, MI, United States.
3
Department of Psychology, Wayne State University, Detroit, MI, United States; Behavioral Pharmacology and Toxicology Laboratory, Wayne State University, Detroit, MI, United States. Electronic address: Scott.Bowen@wayne.edu.

Abstract

Volatile organic solvent abuse continues to be a worldwide health problem, including the neurobehavioral teratogenic sequelae of toluene abuse during pregnancy. Although abuse levels of prenatal toluene exposure can lead to a Fetal Solvent Syndrome, there is little research examining these effects on memory. Consumption of toluene can have detrimental effects on the developing hippocampus which could lead to specific spatial learning and memory deficits. This study used a rat model to determine how prenatal exposure to abuse levels of toluene would affect performance in a spatial learning and memory task, the Morris Water Maze (MWM). Pregnant Sprague-Dawley rats were exposed to 0, 8000 or 12,000ppm (ppm) of toluene for 15min twice daily from gestation day 8 (GD8) through GD20. Male and female offspring (N=104) were observed in the MWM for 5days beginning on postnatal day (PN) 28 and again on PN44. While prenatal toluene-exposed animals did not differ in initial acquisition in the MWM, rats prenatally exposed to 12,000ppm toluene displayed performance deficits during a probe trial and in reversal learning on PN44. Overall, this study indicates that prenatal exposure to repeated inhaled abuse patterns of high concentrations of toluene can impair spatial memory function that persists into adolescence.

KEYWORDS:

organic solvents (toluene); prenatal exposures; rats; spatial learning and memory

[Indexed for MEDLINE]
Free PMC Article
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6.
Hum Exp Toxicol. 2016 Apr;35(4):341-52. doi: 10.1177/0960327115591377. Epub 2015 Jun 15.

Changes in developmental body weight as a function of toluene exposure: A meta-analysis of animal studies.

Author information

1
Department of Psychology, Wayne State University, Detroit, MI, USA Behavioral Pharmacology and Toxicology Laboratory, Wayne State University, Detroit, MI, USA.
2
Department of Psychology, Wayne State University, Detroit, MI, USA.
3
Department of Psychology, Wayne State University, Detroit, MI, USA Behavioral Pharmacology and Toxicology Laboratory, Wayne State University, Detroit, MI, USA Scott.Bowen@wayne.edu.

Abstract

Inhalant abuse is a globally prevalent health issue with particular concerns about substance-abusing pregnant women. In both animal models and clinical case reports of toluene exposure, the primary physiological outcome measure of prenatal inhalant exposure is low birth weight (BW). However, the effect of prenatal toluene exposure on animal BW varies widely in the literature. To clarify this effect and investigate possible design moderators of pup BW, a systematic review and meta-analytic techniques were applied to the existing peer-reviewed animal literature of prenatal and postnatal exposure models to the inhaled solvent toluene. Of 288 studies screened, 24 studies satisfied the inclusion criteria. Evaluation of these studies indicated that toluene exposure was negatively associated with pup BW (d = -0.39), with external inhaled concentration, route of administration, day of weighing, and toluene exposure magnitude moderating this association. Investigators doing animal studies should be cognizant of these factors before investigating the reproductive and developmental outcomes associated with prenatal and postnatal toluene exposure.

KEYWORDS:

Toluene; inhalant; meta-analysis; prenatal

PMID:
26078284
DOI:
10.1177/0960327115591377
[Indexed for MEDLINE]
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7.
Psychopharmacology (Berl). 2015 Jan;232(1):173-84. doi: 10.1007/s00213-014-3651-x. Epub 2014 Jul 5.

Striatal dopamine dynamics in mice following acute and repeated toluene exposure.

Author information

1
Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI, 48202, USA.

Abstract

RATIONALE:

The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene's mechanism of action is unknown.

OBJECTIVE:

The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry.

RESULTS:

Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene's locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25-50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice.

CONCLUSIONS:

These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.

PMID:
24994552
DOI:
10.1007/s00213-014-3651-x
[Indexed for MEDLINE]
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8.
Neuroscience. 2014 Mar 28;263:72-87. doi: 10.1016/j.neuroscience.2014.01.009. Epub 2014 Jan 13.

Separating analgesia from reward within the ventral tegmental area.

Author information

1
Behavioral and Cognitive Neuroscience Program, Department of Psychology, Wayne State University, Detroit, MI 48202, USA.
2
Behavioral and Cognitive Neuroscience Program, Department of Psychology, Wayne State University, Detroit, MI 48202, USA. Electronic address: borszcz@wayne.edu.

Abstract

Activation of the dopaminergic mesolimbic reward circuit that originates in the ventral tegmental area (VTA) is postulated to preferentially suppress emotional responses to noxious stimuli, and presumably contributes to the addictive liability of strong analgesics. VTA dopamine neurons are activated via cholinergic afferents and microinjection of carbachol (cholinergic agonist) into VTA is rewarding. Here, we evaluated regional differences within VTA in the capacity of carbachol to suppress rats' affective response to pain (vocalization afterdischarges, VADs) and to support conditioned place preference (CPP) learning. As carbachol is a non-specific agonist, muscarinic and nicotinic receptor involvement was assessed by administering atropine (muscarinic antagonist) and mecamylamine (nicotinic antagonist) into VTA prior to carbachol treatment. Unilateral injections of carbachol (4μg) into anterior VTA (aVTA) and posterior VTA (pVTA) suppressed VADs and supported CPP; whereas, injections into midVTA failed to effect either VADs or CPP. These findings corroborate the hypothesis that the neural substrates underlying affective analgesia and reward overlap. However, the extent of the overlap was only partial. Whereas both nicotinic and muscarinic receptors contributed to carbachol-induced affective analgesia in aVTA, only muscarinic receptors mediated the analgesic action of carbachol in pVTA. The rewarding effects of carbachol are mediated by the activation of both nicotinic and muscarinic receptors in both aVTA and pVTA. The results indicate that analgesia and reward are mediated by separate cholinergic mechanisms within pVTA. Nicotinic receptor antagonism within pVTA failed to attenuate carbachol-induced analgesia, but prevented carbachol-induced reward. As addictive liability of analgesics stem from their rewarding properties, the present findings suggest that these processes can be neuropharmacologically separated within pVTA.

KEYWORDS:

addiction; analgesia; muscarinic; nicotinic; pain; reward

[Indexed for MEDLINE]
Free PMC Article
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9.
Neurotoxicol Teratol. 2013 Nov-Dec;40:28-34. doi: 10.1016/j.ntt.2013.09.001. Epub 2013 Sep 12.

Repeated toluene exposure increases c-Fos in catecholaminergic cells of the nucleus accumbens shell.

Author information

1
Department of Psychology, Wayne State University, Detroit, MI, United States; The Behavioral Neuroscience of Social Relationships Laboratory, Wayne State University, Detroit, MI, United States. Electronic address: michelletomas@wayne.edu.

Abstract

Toluene is a frequently abused solvent. Previous studies have suggested that toluene acts like other drugs of abuse, specifically on the dopaminergic system in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the mesolimbic pathway. Although changes in dopamine (DA) levels and c-Fos have been observed in both acute and repeated exposure paradigms, the extent to which c-Fos is localized to catecholaminergic cells is unknown. The present study tested the effects of repeated toluene exposure (1000-4000ppm) on locomotor activity and cells containing c-Fos, tyrosine hydroxylase (TH), or both in the core and shell of the NAc, as well as the anterior and posterior VTA. We focused our study on adolescents, since adolescence is a time of great neural change and a time when individuals tend to be more susceptible to drug abuse. In early tests, toluene dose-dependently increased locomotor activity. Repeated exposure to the highest concentration of toluene resulted in sensitization to toluene's effects on locomotor activity. Although the number of cells immunopositive for c-Fos or TH did not significantly differ across groups, cells immunopositive for TH+c-Fos were higher in the NAc shell of animals exposed to 4000ppm than in animals exposed to air (control) or 1000ppm. Taken together, these findings demonstrate that repeated high dose toluene exposure increases locomotor activity as well as activation of catecholaminergic cells in the shell of the NAc.

KEYWORDS:

Nucleus accumbens; Toluene; Tyrosine hydroxylase; Ventral tegmental area; c-Fos

PMID:
24036183
DOI:
10.1016/j.ntt.2013.09.001
[Indexed for MEDLINE]
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