behavior (Tyle, 1988). Aseptic technique is important in the implantation of cannulae or 
pumps and whenever the system must be opened (e.g., to reattach tubing or add drug 
solution). These precautions will greatly reduce morbidity in the animal and prolong the 
useful life of the cannula. 
Inhalation is the most common route of exposure for some agents (e.g., nitrous oxide and 
organic solvents or anesthetics). Administration of some compounds is simplified as with 
nasal sprays, but usually inhalation exposures require specialized experimental chambers or 
equipment to control drug exposure and to protect laboratory personnel and other animals 
from accidental exposure to the airborne chemical (Paule et al., 1992; Taylor and Evans, 
1985). The risk of hypoxia requires attention when drugs are administered by inhalation for 
long durations. Questions of drug abuse by smoking can be modeled with animals (e.g., 
Carroll et al, 1990). 
Studies in which animals are provided the opportunity to self-administer a drug often employ 
the i.v. route, and the animal will be implanted with a chronically indwelling venous cannula. 
Cannulae are common in self-injection studies with rats, monkeys, dogs, and mice (e.g., Lukas 
et al., 1982). They generally are guided subdermally from the implantation site to exit in the 
midscapular region and protected by a vest (see Chapter 4, Experimental Enclosures and 
Physical Restraint). They may remain chronically attached to the infusion system or be 
attached only when the animal is moved to the experimental chamber. Methods for 
intraventricular drug self-administration through cannulae implanted directly into the brain 
also have been developed (Goeders and Smith, 1987). Several drug self-administration 
procedures that use the oral route also have been developed (Meisch and Lemaire, 1993). 
They may employ a specialized drinking spout to regulate the volume of each drink (often 
termed a drinkometer). In these studies, access to a regular supply of drinking water typically 
is not restricted or is restricted only during the experimental session itself so that the drug 
reinforcing efficacy can be determined in the absence of fluid restriction. Choice of route of 
drug delivery for self-administration studies is complexly determined by the purposes of the 
experiment and the nature of the drug and its pharmacokinetics, just to mention the most 
prominent variables. 
To study the effects of chronically administered drugs or toxicants, oral delivery may be 
accomplished by adding the compound to the animal's food or drinking water, as in some 
models of alcoholism (Cunningham and Niehus, 1997) and studies of long-term exposure to 
toxic contaminants of food and water (Cory-Slechta, 1994). Special feeders and water 
canisters (Evans et al., 1986) are available to prevent spillage. When a drug is added to food 
or water, it is important to monitor the animal’s ingestion, both for determining the amount 
of drug received and to identify reduced ingestion resulting from reduced payability. If 
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