Cardiovascular responses to injections of cholinomimetic drugs into the cerebral ventricles of unanaesthetized dogs

Abstract

Summary1. The cardiovascular and behavioural effects of cholinomimetic drugs injected through a cannula chronically implanted into a lateral cerebral ventricle were examined in unanaesthetized dogs.2. Acetylcholine (ACh) (10-20 pg) produced an increase in arterial pressure and heart rate, the dogs became more alert, moved their heads, licked and swallowed and then became drowsy. 3. The responses to ACh were potentiated by intraventricular physostigmine (5 ,ug), were abolished by intraventricular atropine (100 ,ug) but were unaffected by intraventricular mecamylamine (250 ,g). The responses to ACh were reproducible on any one day if injections were given again after a 30 min interval but tolerance developed when ACh was injected repeatedly over periods of several days. 4. Methacholine (40 ,ug) produced similar behavioural and cardiovascular effects to ACh but of a longer duration. The responses to methacholine were abolished by intraventricular atropine (100 ,ug). 5. Nicotine (20-60 ,g) produced a biphasic cardiovascular response of an initial brief pressor response and tachycardia followed by a secondary increase in arterial pressure and heart rate which was greater in magnitude and duration. The secondary cardiovascular effects were associated with restlessness and vomiting.6. The responses to nicotine were abolished by prior injection of mecamylamine (250 ,ug) but were unaffected by atropine (100 ,ug). The responses to nicotine were not reproducible if injections were repeated on the same day but could be again produced if a few days were allowed to elapse between injections.7. An increased heart rate occurred during the pressor response to the cholinomimetic drugs but when a comparable pressor response was produced by intravenous infusion of noradrenaline in the same unanaesthetized dogs pronounced reflex bradycardia resulted. 8. The results indicate that the activation of both muscarinic and nicotinic cholinergic mechanisms leads to cardiovascular and behavioural effects in the conscious dog although the site of action and peripheral mechanisms have not been determined.

Cholinomimetic and anticholinergic drugs used to investigate an acetylcholine hypothesis of affective disorders and stress

“…Central administration of acetylcholine, direct-acting cholinergic agonists, and cholinesterase inhibitors have been shown to consistently increase blood pressure in a variety of animal species, including dogs, cats, and rats [Suh et al, 1975;Lang and Rush, 1973;Day and Roach, 19771. Direct-acting muscarinic agonists which increase blood pressure include acetylcholine itself, carbachol, arecoline, and oxotremorine [Bhawe, 1958;Lang and Rush, 1973;Day and Roach, 19771.…”

“…Direct-acting muscarinic agonists which increase blood pressure include acetylcholine itself, carbachol, arecoline, and oxotremorine [Bhawe, 1958;Lang and Rush, 1973;Day and Roach, 19771. Indirect-acting cholinomimetic agents, including the cholinesterase inhibitors physostigmine, neostigmine, and sarin, also regularly and dramatically increase blood pressure levels in nonanesthetized animals Brezenoff, 19731, and cause a variable response in pulse rate depending on the species studied.…”

Central Adrenoceptors and Cholinoceptors in Cardiovascular Control

“…The central administration of acetylcholine and other cholinomimetic agents in dogs, induced a pressor response and a tachycardia which could be blocked by atropine (Sinha, Dhawan, Chandra & Gupta, 1967;Srimal, Jaju, Sinha, Dixit & Bhargava, 1969;Lang & Rush, 1973). However, variable cardiovascular effects were reported following central administration of cholinomimetic agents in cats (Bhawe, 1958;Armitage & Hall, 1967;Guertzenstein, 1973) and in rats (Brezenoff & Jenden, 1970;Brezenoff, 1972).…”

Cardiovascular Responses Produced by the Injection of Dopamine Into the Cerebral Ventricles of the Unanaesthetized Dog

“…To enable the injection of drugs into the cerebral ventricles, a modified Collison cannula was stereotaxically implanted into the skull to act as a permanent guide tube, by the method of Lang & Rush (1973). The cannula was positioned above the left lateral ventricle, at a point 15 mm anterior to the inter-aural plane and 5 mm lateral to the saggital suture.…”