Indirect dopamine agonists augment the locomotor activating effects of the ?-opioid receptor agonist U-50,488 in preweanling rats

McDougall, Sanders A.; Rodarte-Freeman, Audrey L.; Nazarian, Arbi

doi:10.1002/(sici)1098-2302(199904)34:3<183::aid-dev3>3.0.co;2-1

Cited by 13 publications

(16 citation statements)

References 43 publications

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“…For example, U50,488 (1.6 and 6.4 µg per side) did not affect cocaine-induced repetitive motor movements or stereotyped sniffing on PD 17. In partial contrast to this finding, we have reported that systemic administration of U50,488 caused a dose-dependent reduction in the cocaine-, amphetamine-, and methylphenidate-induced stereotyped sniffing of preweanling rats (McDougall et al, 1999). Based on the present data, it appears that this previously reported U50,488 effect is either (a) not mediated by κ-opioid receptors in the dorsal CPu or (b) U50,488’s locomotor activating effects may have competed with the ability to express stereotyped behaviors (e.g., Bordi et al, 1989).…”

Section: Discussionmentioning

confidence: 78%

“…Preweanling rats, like adults, show enhanced locomotor activity and stereotypy after acute treatment with a psychostimulant drug (Lal and Sourkes, 1973; Sobrian et al, 1975; McDougall et al, 1994, 1999, 2007). In sharp contrast to what is observed in adult rats, κ-opioid agonists do not attenuate cocaine- and amphetamine-induced locomotion during the preweanling period.…”

Section: Introductionmentioning

confidence: 99%

“…Instead, U50,488, when given alone, causes a paradoxical increase in the locomotor activity and wall-climbing of preweanling rats (Jackson and Kitchen, 1989; McLaughlin et al, 1995; Duke et al, 1997;McDougall et al, 1997). Moreover, combined treatment with U50,488 and either cocaine or amphetamine produces a potentiated locomotor response (McDougall et al, 1999). A different pattern of results occurs when stereotyped behaviors are assessed, since κ-opioid agonists reduce cocaine- and amphetamine-induced stereotyped sniffing on postnatal day (PD) 17 (McDougall et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, combined treatment with U50,488 and either cocaine or amphetamine produces a potentiated locomotor response (McDougall et al, 1999). A different pattern of results occurs when stereotyped behaviors are assessed, since κ-opioid agonists reduce cocaine- and amphetamine-induced stereotyped sniffing on postnatal day (PD) 17 (McDougall et al, 1999). The latter result is difficult to interpret, however, because the U50,488-induced increase in locomotor activity probably competes with the expression of stereotyped sniffing.…”

Section: Introductionmentioning

confidence: 99%

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Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

et al. 2010

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Abstractκ-Opioid receptor stimulation attenuates psychostimulant-induced increases in extracellular dopamine in the caudate-putamen (CPu) and nucleus accumbens of adult rats, while reducing cocaine-induced locomotor activity and stereotyped behaviors. Because κ-opioid receptor agonists (e.g., U50,488 or U69,593) often affect the behavior of preweanling rats in a paradoxical manner, the purpose of the present study was to determine whether κ-opioid receptor stimulation differentially affects dopaminergic functioning in the CPu depending on age. In vivo microdialysis was used to determine whether U50,488 (5 mg/kg) attenuates cocaine-induced dopamine overflow in the dorsal CPu on postnatal day (PD) 17 and PD 85. In the microinjection experiment, cocaineinduced stereotyped behaviors were assessed in adult and preweanling rats after bilateral infusions of vehicle or U50,488 (1.6 or 6.4 µg per side) into the CPu. Results showed that U50,488 attenuated the cocaine-induced increases in CPu dopamine overflow on PD 85, while the same dose of U50,488 did not alter dopamine dialysate levels on PD 17. Cocaine also increased stereotyped behaviors (repetitive motor movements, behavioral intensity scores, and discrete behaviors) at both ages, but adult rats appeared to exhibit more intense stereotypic responses than the younger animals. Consistent with the microdialysis findings, bilateral infusions of U50,488 into the dorsal CPu decreased the cocaine-induced stereotypies of adult rats, while leaving the behaviors of preweanling rats unaffected. These results suggest that the neural mechanisms underlying κ-opioid/dopamine interactions in the CPu are not fully mature during the preweanling period. This lack of functional maturity may explain why κ-opioid receptor agonists frequently induce different behavioral effects in young and adult rats.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

et al. 2010

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“…Stimulation of κ-opioid receptors (i.e., the high affinity receptor for dynorphin) also alters locomotion but, in this case, systemically administered κ-opioid agonists (e.g., U50,488 and U69,593) differentially affect the locomotor activity of young and adult animals. In adult rodents, systemic administration of U50,488 or U69,593 depresses locomotor activity and rearing (Ukai and Kameyama, 1985;Jackson and Cooper, 1988;Leyton and Stewart, 1992), while the same compounds robustly increase the locomotor activity and wall-climbing of young rats and mice (Jackson and Kitchen, 1989;Kehoe and Boylan, 1994;Duke et al, 1997;McDougall et al, 1997McDougall et al, , 1999Karper et al, 2000). The basis for this interesting ontogenetic behavioral difference is uncertain, however it may be due to the age-dependent maturation of neural mechanisms mediating locomotion.…”

Section: Introductionmentioning

confidence: 99%

Effects of dorsal striatal infusions of R(−)-propylnorapomorphine on κ-opioid-mediated locomotor activity in the young rat: Possible role of the indirect pathway

et al. 2008

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Stimulation of kappa-opioid receptors in the substantia nigra pars reticulata (SNPR) increases the locomotor activity of young rats: an effect blocked by systemic administration of a D2-like receptor agonist. Based on these initial findings, we proposed that: (a) D2-like receptors in the dorsal striatum are responsible for attenuating kappa-opioid-induced locomotor activity, and (b) the effects of D2-like receptor stimulation are mediated by the indirect pathway, which extends from the dorsal striatum to the SNPR via the globus pallidus (GP) and subthalamic nucleus (STN). To test the first hypothesis, young rats were given a systemic injection (i.p.) of saline or the kappa-opioid receptor agonist (+/-)-trans-U50,488 methanesulfonate salt (U50,488) on postnatal day (PD) 18. Later in the testing session, rats received bilateral infusions of vehicle or the D2-like receptor agonist R(-)-propylnorapomorphine (NPA) into the dorsal striatum, and the ability of NPA to block U50,488-induced locomotor activity was determined. To test the second hypothesis, rats were given sham or bilateral electrolytic lesions of the GP or STN on PD 16. Two days later, saline- and U50,488-induced locomotor activity was measured after systemic (i.p.) administration of vehicle or NPA. As predicted, dorsal striatal infusions of NPA attenuated the U50,488-induced locomotor activity of young rats. Contrary to our expectations, bilateral lesions of the GP or STN did not impair NPA's ability to block U50,488-induced locomotor activity. When considered together, these results suggest that: (a) stimulation of D2-like receptors in the dorsal striatum is sufficient to attenuate the kappa-opioid-mediated locomotor activity of young rats; and (b) the indirect pathway does not mediate the effects of D2-like receptor stimulation in this behavioral model.

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Dynorphin A (1–13) and responsiveness of the newborn rat to a surrogate nipple: Immediate behavioral consequences and reinforcement effects in conditioning

Petrov

Nizhnikov

Varlinskaya

et al. 2006

Behavioural Brain Research

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Indirect dopamine agonists augment the locomotor activating effects of the ?-opioid receptor agonist U-50,488 in preweanling rats

Cited by 13 publications

References 43 publications

Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

Effects of dorsal striatal infusions of R(−)-propylnorapomorphine on κ-opioid-mediated locomotor activity in the young rat: Possible role of the indirect pathway

Dynorphin A (1–13) and responsiveness of the newborn rat to a surrogate nipple: Immediate behavioral consequences and reinforcement effects in conditioning

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