A quantitative estimate of the role of striatal D-2 receptor proliferation in dopaminergic behavioral supersensitivity: The contribution of mesolimbic dopamine to the magnitude of 6-OHDA lesion-induced agonist sensitivity in the rat

Mandel, Ronald J.; Hartgraves, Stanley L.; Severson, James A.; Woodward, John J.; Wilcox, Richard E.; Randall, Patrick K.

doi:10.1016/0166-4328(93)90151-f

Cited by 21 publications

(11 citation statements)

References 31 publications

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“…It is also consistent with a D 1 /D 2 interactional model proposed to account for the observation that in mice bearing unilateral striatonigral lesions, the maximum number of rotations induced by apomorphine is increased by sulpiride pretreatment, without a change in potency of apomorphine to induce rotations (Randall 1988;Mandel et al 1993). The second possibility is consistent with findings that chronic administration of a number of psychostimulants induces immediate-early genes and second messengers (Graybiel et al 1990;Dragunow et al 1991;Terwilliger et al 1991;Chen et al 1995;Nestler 1995).…”

Section: Increase In Efficacysupporting

confidence: 89%

Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency

et al. 1997

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This study examines whether behavioural sensitization to the dopamine agonist, quinpirole, reflects an increase in the drug's potency and/or efficacy to induce locomotion, and how these parameters are influenced by environmental context. Three experiments were conducted in which animals received either chronic quinpirole (10 x 0.5 mg/kg, twice weekly) or saline injections in either the home cage environment, an alternate environment or the testing environment (activity monitors), followed by a dose-response test for the expression of sensitization in the activity monitors. Compared to the acute dose-response relationship, chronic quinpirole increased the maximum response. This increase in efficacy was significantly higher in animals treated with quinpirole in a non-home cage environment compared to those that received chronic treatment in the home cage. A leftward shift in the dose-effect function was observed only in animals with prior drug experience in the testing environment. Results indicate that locomotor sensitization to quinpirole reflects an environment-modulated increase in the drug's efficacy, and an environment-dependent increase in drug potency. Efficacy and potency may be subject to sensitization by non-associational and associational mechanisms, respectively.

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Section: Increase In Efficacysupporting

confidence: 89%

Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency

et al. 1997

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“…If the 2-hydroxyestradiol-associated decrease in dopamine in the prefrontal cortex causes supersensitization of postsynaptic dopamine 2-type receptors, at the same time that 2- hydroxyestradiol (or the parent compound, estradiol) is increasing the number of these receptors, then 2-hydroxyestradiol could be creating conditions that exacerbate bingeing. Supporting this idea, the phenomenon of simultaneous supersensitivity and increased number of dopamine 2- type receptors has been shown with 6-OHDA lesions in adult animals (Mandel et al 1993; Kostrzewa 1995). Importantly, activation of post-synaptic dopamine 2-type receptors in the prefrontal cortex inhibits the firing of glutamatergic pyramidal cells (Tseng and O'Donnell 2007), which project to the nucleus accumbens (Brog et al 1993; Carr et al 1999).…”

Section: Discussion-studymentioning

confidence: 73%

2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal cortical dopamine in male rats

Babbs

Unger

Corwin

2013

Hormones and Behavior

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Women are more likely to suffer from a bingeing-related eating disorder, which is surprising, since estradiol reduces meal size and is associated with reduced binge frequency. This apparent contradiction may involve the estradiol metabolite, 2-hydroxyestradiol. We previously reported that female rats had faster escalations in shortening intake during the development of bingeing than did males, but acute administration of 2-hydroxyestradiol increased the intake of vegetable shortening to a greater extent in male rats once bingeing was established. Here, we report two separate studies that follow up these previous findings. In the first, we hypothesized that chronic exposure to 2-hydroxyestradiol would promote escalation of bingeing during binge development in ovariectomized female rats. In the second, we hypothesized that acute exposure to 2-hydroxyestradiol would enhance dopamine signaling in the prefrontal cortex after bingeing was established in male rats. In study 1, non-food-deprived female rats were separated into 3 groups: ovariectomized (OVX) with chronic 2-hydroxyestradiol supplementation (E), OVX with vehicle supplementation (O), and intact with vehicle (I). Each group was given access to an optional source of dietary fat (shortening) on Mon, Wed, and Fri for four weeks. 2-hydroxyestradiol supplementation prevented OVX-induced weight gain and enhanced escalation of shortening intake over the four-week period (ps < 0.05). Additionally, in week 4, rats in the E group ate significantly more shortening than I controls, less chow than either the O or I group, and had a higher shortening to chow ratio than O or I (ps < 0.05). Study 2 indicated that acute injection of 2-hydroxyestradiol abolished shortening-evoked dopamine efflux in the prefrontal cortex of bingeing male rats (p < 0.05). Together, these studies indicate that 2-hydroxyestradiol can exacerbate bingeing as it develops and can suppress dopamine signaling in the prefrontal cortex once bingeing is established.

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“…Furthermore, the upregulation of the postsynaptic D 2 receptor has been described in the literature. This change of BP ND reflects the supersensitivity of the D 2 receptors several weeks after dopaminergic denervation in the lesioned striatum (Miller and Beninger, 1991;Ungerstedt, 1971), which is partly due to an increase in receptor density (Mandel et al, 1993;Sossi et al, 2009). These results were confirmed by Doudet et al (2002), in a study on MPTP-treated monkeys, in which the increase in [ 11 C]raclopride BP ND was due to an increase in B avail without affecting appK d .…”

Section: Assessment Of L-dopa-induced Aimsmentioning

confidence: 73%

Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

et al. 2012

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A quantitative estimate of the role of striatal D-2 receptor proliferation in dopaminergic behavioral supersensitivity: The contribution of mesolimbic dopamine to the magnitude of 6-OHDA lesion-induced agonist sensitivity in the rat

Cited by 21 publications

References 31 publications

Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency

Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency

2-Hydroxyestradiol enhances binge onset in female rats and reduces prefrontal cortical dopamine in male rats

Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

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