Discriminative stimulus properties of the vasodilator, hydralazine: differential generalization with alpha 1 and alpha 2 adrenoreceptor drugs.
1. Male albino rats were trained to an operant procedure of lever pressing on an FR-10 schedule of food reinforcement to respond on one lever located on one side of the food cup after an injection of hydralazine (1,25 mg/kg), and to respond on an alternate lever located on the other side of the food cup after an injection of saline. 2. Seven out of ten rats learned the hydralazine-saline discrimination to the rigid criterion of selecting the correct lever for reinforcement on ten consecutive sessions. 3. The elicitation of the discriminative stimulus was dose-dependent (r = 0,98; p less than .001) with 100, 43, and 14% of the subjects selecting the hydralazine lever following hydralazine doses of 1,25; 0,32 and 0,08 mg/kg, respectively (ED50, 0,28 mg/kg). 4. A reduction in response rate and blood pressure was noted only at the 1.25 mg/kg dose. 5. No tolerance to the hypotensive effect of hydralazine was found. 6. In generalization tests, prazosin, an alpha 1 antagonist, was found to produce a dose-dependent generalization to hydralazine (ED50, 1, 25 mg/kg) while clonidine, an alpha 2 agonist, did not generalize. 7. These data indicate that hydralazine produces a discriminable interoceptive stimulus exact site of action of which is not known.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology*; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D006830:Hydralazine; D003000:Clonidine; D011224:Prazosin