Brain temperature fluctuations during passive vs. active cocaine administration: clues for understanding the pharmacological determination of drug-taking behavior.

While it is generally assumed that cocaine self-administration (SA) is determined and maintained by the pharmacological actions of cocaine in the brain, it is also a drug-motivated and drug-reinforced goal-directed behavior, which is determined by concurrent learning and behavioral performance. To dissociate the contributions of pharmacological and behavioral factors to cocaine SA, it is important to compare cocaine SA with its pharmacological copy, passive intravenous (iv) cocaine administration. This approach was employed in the present study with respect to brain temperatures, a dynamic parameter that reflects metabolic neural activity and shows consistent fluctuations during cocaine SA. Passive cocaine injections performed with the same dose/pattern as SA induced brain temperature fluctuations similar in many ways to those in behaving animals. The initial passive drug administration of a session elevated brain temperature, while subsequent repeated injections were associated with biphasic temperature fluctuations that maintained at a relatively stable plateau. Although the magnitude of these fluctuations was twofold smaller than in behaving animals, passive animals had the same pattern; brain temperatures transiently decreased after cocaine injection, then increased, and were inhibited again by the next cocaine infusion. In contrast to self-administering animals, rats exposed to passive cocaine injections had significantly lower basal temperatures and never showed gradual temperature increases preceding the initial injection. Striking differences in brain temperature dynamics seen in the beginning of a session suggest that during the development of drug-taking behavior the initial cocaine-induced neural activation becomes transformed into behavior-related "anticipatory" neural activation (motivational arousal) that fuels drug seeking and results in the initial drug intake. While this activation is triggered by drug-related cues and enhanced by the initial cocaine intake, subsequent highly cyclical cocaine intakes appear to be primarily pharmacologically determined.