Fluctuations in neural activity during cocaine self-administration: clues provided by brain thermorecording.

Since metabolic neural activity is accompanied by heat release, measurement of local brain temperature offers a method for assessing alterations in neural activity. This approach, continuous monitoring of local brain (ventral tegmental area, ventral striatum, and hippocampus) and body (temporal muscle) temperature, was used to study intravenous cocaine self-administration in trained rats. The first self-administration of a session was preceded by a strong temperature increase that continued after the drug infusion. After peaking at the time of the second self-administration, temperature plateaued (+0.7 degrees C) with biphasic fluctuations (+/-0.10-0.15 degrees C) around each subsequent self-administration. Temperature gradually increased before and for 30-50 s after the lever-press, but then abruptly decreased to a minimum at 180-240 s, when it began to increase to reach another peak immediately after the next lever-press. Doubling the dose of injected cocaine significantly potentiated the post-cocaine temperature decrease and increased time to the next lever-press. In contrast to drug-reinforced lever-presses, temperatures phasically increased after non-reinforced lever-presses and at the end of a session when the lever was blocked and the rat was hyperactive, trying to reach the inaccessible lever. While temperature changes in each recording location were generally correlative, the initial temperature elevation was stronger in all brain structures than in muscle and ventral striatum was the structure that showed the most pronounced and consistent temperature fluctuations. These data suggest a generalized brain activation associated with cocaine-seeking and cocaine-taking behavior with its phasic fluctuations around individual drug self-injections. While the initial component of brain activation preceding the first lever-press for cocaine is internally determined and closely related to behavioral search, subsequent biphasic fluctuations in neural activity associated with repeated drug intakes appear to be drug-mediated. Cocaine-induced potentiation of monoamine transmission is a possible factor for gradual increases in neural activity that drive cocaine seeking, while a rapid, brain concentration-dependent action on Na(+) transport (local anesthetic action) is the most probable factor determining an abrupt, transient cessation of neural activation associated with cocaine reward.