Behavioral effects in the rat of dihydrexidine, a high-potency, full-Efficacy D1 dopamine receptor agonist

Kirwin J. Darney, Mark H. Lewis, William K. Brewster, David E. Nichols, Richard Mailman

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Dihydrexidine (trans-10,11-dihydroxy-5,6,6a,7,8, 12b-hexahydrobenzo[a]phenanthridine) was reported recently to be the first full efficacy, potent D1 receptor agonist, but one also having some potency for D2 receptors. This study reports the effects of dihydrexidine on behavior of the rat. In study 1, the dose-response relationships of dihydrexidine (0.3 to 30 mg/kg) to various behaviors were assessed using direct observations. The frequency of three behaviors (grooming, sniffing, and locomotion) was significantly increased by this drug. The dose-response curve for drug-induced grooming approximated an inverted U shape. Dihydrexidine increased locomotion at two of the higher doses (3 and 30 mg/kg), and increased sniffing at doses ≥1.0 mg/kg. Other behavioral topographies, such as licking, gnawing, and rearing, were not systematically affected by drug administration. Also, there was no indication of convulsion in any dihydrexidine-treated rat. In study 2, rats were pretreated with either the selective D1 antagonist SCH23390 or the selective D2 antagonist remoxipride prior to receiving dihydrexidine. SCH23390 antagonized the effects of dihydrexidine on grooming, locomotion, and sniffing. Conversely, remoxipride blocked dihydrexidine-induced locomotion, but had no effect on dihydrexidine-induced grooming or sniffing. Numerous behaviors are believed to be mediated by the interactions of D1 and D2 receptors. These data indicate that dihydrexidine can be an important tool for characterizing both the behavioral actions of D1 receptors, and the nature of D1/D2 interactions in mammalian brain. In addition, its high potency and full efficacy at D1 receptors, coupled with its significant D2 properties, may provide specific utility in certain clinical situations.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalNeuropsychopharmacology
Volume5
Issue number3
StatePublished - Nov 1991

Fingerprint

Dopamine Agonists
Grooming
Locomotion
Remoxipride
Phenanthridines
dihydrexidine
Pharmaceutical Preparations
Seizures

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Darney, Kirwin J. ; Lewis, Mark H. ; Brewster, William K. ; Nichols, David E. ; Mailman, Richard. / Behavioral effects in the rat of dihydrexidine, a high-potency, full-Efficacy D1 dopamine receptor agonist. In: Neuropsychopharmacology. 1991 ; Vol. 5, No. 3. pp. 187-195.
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abstract = "Dihydrexidine (trans-10,11-dihydroxy-5,6,6a,7,8, 12b-hexahydrobenzo[a]phenanthridine) was reported recently to be the first full efficacy, potent D1 receptor agonist, but one also having some potency for D2 receptors. This study reports the effects of dihydrexidine on behavior of the rat. In study 1, the dose-response relationships of dihydrexidine (0.3 to 30 mg/kg) to various behaviors were assessed using direct observations. The frequency of three behaviors (grooming, sniffing, and locomotion) was significantly increased by this drug. The dose-response curve for drug-induced grooming approximated an inverted U shape. Dihydrexidine increased locomotion at two of the higher doses (3 and 30 mg/kg), and increased sniffing at doses ≥1.0 mg/kg. Other behavioral topographies, such as licking, gnawing, and rearing, were not systematically affected by drug administration. Also, there was no indication of convulsion in any dihydrexidine-treated rat. In study 2, rats were pretreated with either the selective D1 antagonist SCH23390 or the selective D2 antagonist remoxipride prior to receiving dihydrexidine. SCH23390 antagonized the effects of dihydrexidine on grooming, locomotion, and sniffing. Conversely, remoxipride blocked dihydrexidine-induced locomotion, but had no effect on dihydrexidine-induced grooming or sniffing. Numerous behaviors are believed to be mediated by the interactions of D1 and D2 receptors. These data indicate that dihydrexidine can be an important tool for characterizing both the behavioral actions of D1 receptors, and the nature of D1/D2 interactions in mammalian brain. In addition, its high potency and full efficacy at D1 receptors, coupled with its significant D2 properties, may provide specific utility in certain clinical situations.",
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Behavioral effects in the rat of dihydrexidine, a high-potency, full-Efficacy D1 dopamine receptor agonist. / Darney, Kirwin J.; Lewis, Mark H.; Brewster, William K.; Nichols, David E.; Mailman, Richard.

In: Neuropsychopharmacology, Vol. 5, No. 3, 11.1991, p. 187-195.

Research output: Contribution to journalArticle

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