The Ability of Environmental Context to Facilitate Psychomotor Sensitization to Amphetamine Can Be Dissociated from Its Effect on Acute Drug Responsiveness and on Conditioned Responding

Abstract

Doses of amphetamine or cocaine that fail to induce psychomotor sensitization when given to a rat in its home NO . 6 Psychomotor Sensitization to Amphetamine 681 increasing attention because the neural changes underlying sensitization to drugs of abuse may contribute to addiction (Lett 1989;Piazza et al. 1989;Robinson and Berridge 1993). In studying the conditions that facilitate or retard sensitization we have found that the context in which drugs are administered has a large effect on their ability to induce psychomotor sensitization (Badiani et al. 1995a(Badiani et al. , 1995bRobinson et al. 1998, for review). For example, doses of amphetamine, cocaine, or morphine that fail to induce psychomotor sensitization when given in the home cage, induce robust sensitization when given in a distinct and relatively novel environment (Badiani et al. 2000b;Browman et al. 1998aBrowman et al. , 1998bCrombag et al. 1996). The mechanisms responsible for the facilitation of sensitization by a distinct environment are not known, but it is tempting to relate them to associative learning processes (Badiani et al. 1995a(Badiani et al. , 1995b. Indeed, it has been suggested that sensitization may be the result of a progressive increase in the ability of treatment-related stimuli to elicit a conditioned response (CR), which adds to the unconditioned drug response (UR) (Hinson and Poulos 1981;Pert et al. 1990;Tilson and Rech 1973). If this hypothesis is correct, manipulations that degrade the ability of contextual stimuli to acquire conditioned stimulus (CS) properties should attenuate the facilitation of sensitization that occurs when drugs are administered in a distinct environment. Increasing the interval between presentation of the would-be CS and the unconditioned stimulus (US) is known to impair conditioning (Kimble 1947;Pickens and Crowder 1967). Therefore, in the present experiment we studied the effect of increasing the CS-US interval on the development of sensitization produced by amphetamine, by habituating rats to the test environment prior to drug administration. The psychomotor stimulant effects of repeated intravenous (i.v.) injections of amphetamine were assessed by quantifying rotational behavior in rats with a unilateral 6-OHDA lesion. Injections were given (1) in the absence of any environmental stimuli predictive of drug administration (HOME groups); (2) immediately after rats were placed into a distinct environment (NOVEL groups); or (3) in a distinct environment, but after either 1 or 6-8 hr of habituation to that environment (1 hr and 6-8 hr HABITUA-TION groups). Intravenous injections of amphetamine were given using remote-controlled syringe pumps. Thus, amphetamine was administered in the absence of the aversive stimuli associated with other routes of experimental drug administration (e.g., appearance of an experimenter, handling, needle jab). MATERIALS AND METHODS Subjects and Behavioral MeasureMale Sprague-Dawley rats (Harlan Sprague Dawley, Indianapolis, IN), weighing 200-225 g on arrival were individu...

Ethological analyses of crayfish behavior: a new invertebrate system for measuring the rewarding properties of psychostimulants

“…Following approach to an aquarium corner, several amphetamine-treated crayfish carried out repeated bouts of grooming, particularly of the ventral side (see Table 1 and website). The PCA revealed no differences in the amount of time spent grooming (F [3,16] = 0.16, P = 0.922). However, due to a combination of small sample sizes and the relatively short amount of time it took to complete a single bout of grooming this particular measure may have been insensitive to drug effects.…”

“…The duration of the cocaine-induced posture was dose dependent ( Fig. 2B; F [3,16] = 156.11, P < 0.001). Similar posturing occurred after intra-pericardial cocaine infusions (during the CPP experiments) although it took place with a slower onset and more rapid disappearance.…”

“…PC2 differentiated amphetamine-treated crayfish from controls (F [3,16] = 11.08, P < 0.001). Explore and forward walking had large factor loadings on PC2, and correlated negatively in such a way that crayfish either spent a large amount of the observation period walking about the aquarium or instead explored the perimeter with their antennae.…”

“…Principal component values for PC1 were distributed evenly across all experimental groups (F [3,16] = 0.48, P = 0.703).…”

“…Amphetamine-injected crayfish spent significantly more time exploring the corners of the aquarium (mean ± S.E. of the total observation time; control, 12.9 ± 6.49%; 2.5 μg/g, 33.1 ± 9.78%; 5.0 μg/g, 51.9 ± 9.74%; 10.0 μg/g, 41.1 ± 10.29%; F [3,16] = 6.62, P < 0.01).…”