The discriminative properties of the D1 dopamine agonist dihydrexidine in the rat.
Amphetamine/pharmacology; Animals; Apomorphine/pharmacology; Benzazepines/pharmacology; Cocaine/pharmacology; Discrimination (Psychology); Dopamine Agonists/pharmacology; Dopamine D1/*agonists; Dose-Response Relationship; Drug; Male; Phenanthridines/*pharmacology; Rats; Receptors; Sprague-Dawley
The objective of this study was to train rats to discriminate the interoceptive stimuli produced by a selective dopamine D1 agonist. Fourteen male Sprague-Dawley rats acquired the discrimination of the fully effective, high potency, D1 agonist dihydrexidine (DHX) within 20 sessions using a training dose of 3.0 mg/kg. DHX (0.75-4.5 mg/kg) dose-dependently increased DHX-appropriate responding with an ED50 = 1.44 mg/kg. The selective D1 agonist SKF 38398 (2.0-8.0 mg/kg) dose-responsively generalized with an ED50 = 3.54 mg/kg; significantly less potent than DHX. The selective D1 antagonist SCH 23390 (0.06-0.12 mg/kg) dose-responsively decreased DHX-appropriate discriminative performance. These data would indicate that DHX is a selective D1 agonist that may allow for testing of the selectivity of other putative D1 agonists in this experimental procedure. Administration of non-selective dopaminergically active drugs, including apomorphine, amphetamine and cocaine, were each shown to produce intermediate
Schechter M D
Psychopharmacology
1995
1995-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/bf02246057" target="_blank" rel="noreferrer noopener">10.1007/bf02246057</a>
Role of dopamine D1 receptors in cocaine lethality.
Animals; Benzazepines/pharmacology; Cocaine/*toxicity; Dopamine Agonists/pharmacology; Dopamine D1/agonists/antagonists & inhibitors/*drug effects; Female; Inbred Strains; Lethal Dose 50; Male; Mice; Phenanthridines/pharmacology; Receptors; Sex Characteristics
One group of heterogeneously bred HS mice was assigned to test coadministration of the selective D1 antagonist SCH 23390 with a dose of cocaine (95 mg/kg) that was observed to produce 80% lethality, whereas a second group was tested by cotreatment with the newly developed full-efficacy D1 agonist dihydrexidine (DHX) and a dose of (60 mg/kg) cocaine previously shown to be nonlethal. The mice in the former group displayed decreased lethality going from 80% with coadministered vehicle to 15% after pretreatment with the highest dose (0.45 mg/kg) of SCH 23390. In the other group of mice there was no lethality seen when vehicle or 10 mg/kg DHX was coadministered with 60 mg/kg cocaine, but a dose-responsive increase in lethality with increasing DHX doses; the maximal lethality of 80% occurred when 25 mg/kg DHX was coadministered with cocaine. These results confirm the effects of D1 antagonism decreasing cocaine lethality as reported previously when rats were used, and extend the findings to D1 agonism; both observations evidence a role for the D1 receptor in the lethal effects, be they central, cardiopulmonary, or anesthetic, of cocaine.
Schechter M D; Meehan S M
Pharmacology, biochemistry, and behavior
1995
1995-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0091-3057(95)00046-y" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(95)00046-y</a>