BEHAVIORAL-EFFECTS OF HISTAMINE H-1 ANTAGONISTS - COMPARISON WITH OTHER DRUGS AND MODIFICATION BY HALOPERIDOL

  • 1 May 1988
    • journal article
    • research article
    • Vol. 245  (2) , 471-478
Abstract
The behavioral effects of several histamine H1 antagonists were compared in groups of squirrel monkeys trained to respond under fixed-interval schedules involving response-produced shock or termination of a stimulus associated with shock. Low to intermediate doses of the conventional H1 antagonists chlorpheniramine (up to 3.0 mg/kg), diphenhydramine (up to 1.0 or 3.0 mg/kg), pyrilamine (up to 3.0 mg/kg) and tripelennamine (up to 0.3 or 1.0 mg/kg) produced dose-related increases in response rate under all conditions in which they were studied; higher doses either increased responding less or decreased it. In contrast, a wide range of doses of the novel H1 antagonists AHR 11325 (1.0-30.0 mg/kg), astemizole (up to 10.0 mg/kg) and loratadine (up to 17.0 mg/kg) usually had little effect on responding, although decreases in response rate accompanied by emesis were observed after the highest doses in some monkeys. Other H1 antagonists including phenindamine (0.03-17.0 mg/kg), promethazine (0.03-5.6 mg/kg) and terfenadine (0.1-10.0 mg/kg) had different effects in individual subjects (i.e., dose-related increases in response rate in some monkeys and either little change or dose-related decreases in responding in other monkeys). The dopamine uptake inhibitors cocaine (0.01-1.0 mg/kg) and bupropion (0.1-10.0 mg/kg) had behavioral effects similar to those of chlorpheniramine, diphenhydramine, pyrilamine, and tripelennamine, whereas the muscarinic antagonist atropine (0.03-1.0 mg/kg), the serotonin 5-hydroxytryptamine1/5-hyeroxytryptamine2 antagonist cyproheptadine (0.03-1.0 mg/kg), the norepinephrine uptake inhibitor desmethylimipramine (0.03-3.0 mg/kg) and the benzodiazepine diazepam (0.3-30.0 mg/kg) produced only dose-related decreases in response rate. Haloperidol (0.001 or 0.01 mg/kg) attenuated the rate-increasing effects of pyrilamine and cocaine and, to a lesser extent, of diphenhydramine and bupropion. Prazosin (0.1 or 0.3 mg/kg) did not appreciably alter the rate-increasing effects of either pyrilamine or cocaine. The results are consistent with the view that the rate-increasing effects of chlorpheniramine, diphenhydramine, pyrilamine, and tripelennamine reflect neurochemical actions other than their ability to block central histamine receptors. The results suggest further that these effects may involve a dopaminergic component of action.