Dopamine Auto- and Postsynaptic Receptors: Electrophysiological Evidence for Differential Sensitivity to Dopamine Agonists

Skirboll, L.R.; Grace, AA; Bunney, Benjamin S.

doi:10.1126/science.482929

Cited by 491 publications

(138 citation statements)

References 18 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…Three lines of evidence indicate that the 0.05 mg/kg dose is relatively selective for pre-over postsynaptic D2-like receptors. First, electrophysiological studies show that dopamine autoreceptors (Starke, 1981) are 3-10 times more sensitive to dopamine agonists, including QNP, than dopamine receptors located on postsynaptic cells in the striatum or the nucleus accumbens (Kelland et al, 1990;Skirboll et al, 1979;White and Wang, 1986). The typical autoreceptor effects, such as near total inhibition of spontaneous cell firing by midbrain dopamine neurons, can be produced with doses of QNP as low as 0.03 mg/kg (Mottola et al, 2002;Pitts et al, 1995).…”

Section: Drugsmentioning

confidence: 99%

“…The mode of action by which a dopamine agonist could produce this shut-down includes stimulation of somatodendritic D2 autoreceptors to reduce dopamine cell firing (Skirboll et al, 1979), stimulation of D2 autoreceptors on presynaptic terminals to inhibit dopamine release (Rouge-Pont et al, 2002), or both. Consequently, the loss of drug-depressive effects found in sensitization may reflect induction by chronic agonist treatment of autoreceptor subsensitivity (Antelman and Chiodo, 1983;Castro et al, 1985;Muller and Seeman, 1979;Richtand et al, 2001) and in particular of impulseregulating and/or release-regulating D2 autoreceptors.…”

Section: A Model Of Qnp Sensitizationmentioning

confidence: 99%

See 1 more Smart Citation

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Perreault

Graham

Bisnaire

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

To assess whether the development and expression of behavioral sensitization to the dopamine D2/D3 agonist quinpirole (QNP) is influenced by coadministration of the kappa opioid receptor agonist U69593, rats received every 3-4 days for a total of 10 treatments an injection of U69593 (0.3 mg/kg) together with an injection of either a postsynaptic (0.5 mg/kg) or a presynaptic dose of QNP (0.05 mg/ kg); locomotor activity was measured after each treatment. Control rats were injected as appropriate with QNP, U69593, and vehicle/ saline. Following chronic treatment, dose-response profiles to QNP were obtained to assess the expression of sensitization; the effect of U69593 on locomotor activity in animals already sensitized to QNP was also assessed. Results showed that cotreatment of U69593 with a postsynaptic dose of QNP doubled the speed and magnitude of sensitization to QNP, while U69593 cotreatment with a presynaptic dose of QNP switched the effects of QNP from locomotor depression to locomotor sensitization. However, U69593 cotreatment with a presynaptic dose of QNP changed a different set of measures of sensitization than did cotreatment with a postsynaptic dose of the dopamine agonist. Together, findings suggest that sensitization to QNP is not a unitary phenomenon but has components that are relatively independent, mediated by distinct pre-and postsynaptic mechanisms and modulated by kappa receptor activity.

show abstract

Section: Drugsmentioning

confidence: 99%

Section: A Model Of Qnp Sensitizationmentioning

confidence: 99%

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Perreault

Graham

Bisnaire

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…These opposing effects have been explained by the postulate that DA agonists act at different DA receptors to induce these effects i.e. at presynaptically located DA autoreceptors and postsynaptic DA receptors respectively (StriSmbom, 1976;Skirboll et al, 1979;Costall et al, 1981). These behavioural effects of apomorphine occur not only after subcutaneous (s.c.) treatment but also after local injection into * To whom all correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

The hypomotility elicited by small doses of apomorphine seems exclusively mediated by dopaminergic systems in the nucleus accumbens

Radhakishun

Ree

1987

European Journal of Pharmacology

View full text Add to dashboard Cite

The reduction of motor activity elicited in rats by a subcutaneous injection of a small dose of apomorphine was reversed by pretreatment of the nucleus accumbens with haloperidol (10 pg), sulpiride (10 pg) or desenkephalin--f-endorphin (DE),E) (100 pg or 10 ng). These doses of the compounds did not change motor activity in placebo-treated rats. Pretreatment of the nucleus caudatus with the same neuroleptics or DE'rE did not diminish the effect of subcutaneously administered low doses of apomorphine. A small dose of apomorphine decreased motor activity when it was injected directly into the nucleus accumbens. This effect was dose dependently antagonized by subcutaneous pretreatment with DE~,E. It is suggested that the hypoactivity elicited by small doses of apomorphine is exclusively mediated by dopaminergic systems in the nucleus accumbens.

show abstract

“…Between withdrawal days 1 and 5, rats in each pretreatment groups were injected with single daily subcutane-ous injections of one of the following: (1) 2 ml/kg saline, (2) 100 g/kg apomorphine, (3) 0.5 mg/kg SCH 39166 followed 30 minutes later by 100 g/kg apomorphine, (4) 30 g/kg quinpirole, or (5) 100 g/kg quinpirole. The low doses of apomorphine and quinpirole were chosen for selective stimulation of DA autoreceptors, which are generally agreed to be more sensitive to agonists than the postsynaptic receptors (Nickolson 1981;Skirboll et al 1979;Jeziorski and White 1989;Lee and Ellinwood 1989). Similar "low-dose" strategies have been previously used to examine effects of repeated autoreceptor stimulation on DA functions (e.g., Mereu et al 1987;Jeziorski and White 1989).…”

Section: Animals and Pretreatmentmentioning

confidence: 99%

“…In the SNC, stimulation of DA receptors with "autoreceptor-selective" doses of apomorphine or quinpirole (Nickolson 1981;Skirboll et al 1979;Jeziorski and White 1989;Lee and Ellinwood 1989) between withdrawal days 1 and 5 reverses the reductions in the number of active DA neurons. Furthermore, the normalization of spontaneous firing activity seen with apomorphine is not inhibited by the co-administration of the D 1 antagonist SCH 39166.…”

Section: Changes Following Continuous Cocaine Infusionmentioning

confidence: 99%

Altered Activity of Midbrain Dopamine Neurons Following 7-Day Withdrawal from Chronic Cocaine Abuse is Normalized by D2 Receptor Stimulation During the Early Withdrawal Phase

Lee

Gao

Davidson

et al. 1999

Neuropsychopharmacology

View full text Add to dashboard Cite

Using in vivo single-unit recording in rats, we compared the effects of continuous cocaine infusion via minipump or single daily injections (both 40 mg/kg/d ϫ 14 days, SC) on the activity of putative dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA).The two opposite behavioral outcomes in animal models of chronic cocaine or amphetamine abuse are sensitization and tolerance, which are induced by intermittent injection or continuous infusion, respectively (Inada et al. 1992;King et al. 1992;Lau et al. 1991;Post and Rose 1976;Reith et al. 1987). Behavioral sensitization has been hypothesized as a model of the increasing reinforcing effects of cocaine in humans, especially during the early stages of abuse (Kilbey and Ellinwood 1977;Post and Contel 1983;Robinson and Berridge 1993;Mendrek et al. 1998;Kalivas 1995). Tolerance, on the other hand, may provide an animal model for elucidating time-dependent loss of mental and physical energy associated with stimulant withdrawal after multi-day high-dose, compulsive binges (Gawin and Ellinwood 1988;Weiss et al. 1995).The two dosing regimens for the above stimulants are also associated with distinctive electrophysiological changes in the potency of dopamine (DA) agonists in inhibiting activity of DA neurons in the substantia nigra zona compacta (SNC, which projects primarily to the dorsal striatum) and ventral tegmental area (VTA, which projects to the ventral striatum and prefrontal cortex). In the SNC, for example, while both continuous (Kamata and Rebec 1984;Ellinwood and Lee 1983;Lee and Ellinwood 1989), the mechanisms underlying this subsensitivity are different (Pitts et al. 1989(Pitts et al. , 1993Lee et al. 1997). For intermittent injections (which lead to phasically high levels of cocaine) an enabling by a D 1 -dependent mechanism appears to play a key role in the agonist subsensitivity (Pitts et al. 1989(Pitts et al. , 1993Lee et al. 1997), whereas a direct change in D 2 autoreceptor sensitivity might underlie the subsensitivity following continuous infusion (Lee et al. 1997). In contrast to the SNC, the findings in the VTA are most consistent with autoreceptor subsensitivity (Henry et al. 1989;Lee et al. 1997;White et al. 1995) and normosensitivity (Lee et al. 1997) 1 day after withdrawal from intermittent and continuous regimens, respectively. The differential effects of chronic cocaine treatments on the VTA and SNC may be reflective of their different afferent connections as well as differences in their respective DA receptor populations.Following a longer withdrawal period (e.g., 7 days), intermittent injections are generally associated with normosensitivity of the SNC and VTA DA neurons to DA agonists (Henry et al. 1989;White et al. 1995;Lee et al. 1997). Continuous infusion is also associated with a normosensitivity of the VTA DA neurons following 7-day withdrawal. However, as we have demonstrated previously, the SNC DA neurons become supersensitive to apomorphine (Ellinwood and Lee 1983;Lee and Ellinwood 1989...

show abstract

Dopamine Auto- and Postsynaptic Receptors: Electrophysiological Evidence for Differential Sensitivity to Dopamine Agonists

Cited by 491 publications

References 18 publications

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

The hypomotility elicited by small doses of apomorphine seems exclusively mediated by dopaminergic systems in the nucleus accumbens

Altered Activity of Midbrain Dopamine Neurons Following 7-Day Withdrawal from Chronic Cocaine Abuse is Normalized by D2 Receptor Stimulation During the Early Withdrawal Phase

Contact Info

Product

Resources

About