Comparison of two intracranial self-stimulation (ICSS) paradigms in C57BL/6 mice: head-dipping and place-learning.

A variety of intracranial self-stimulation (ICSS) paradigms have been utilized for investigations of reward. Among them, nose-poking and spatial-preference paradigms are known to be relatively more resistant to the effects of drug-induced motor-deficits in rat studies, although these two ICSS paradigms have not been directly compared in previous studies. In the present study, head-dipping and place-learning (forms of nose-poking and spatial-preference tasks, respectively) paradigms with lateral hypothalamus stimulation were systematically analyzed using C57BL/6 mice in the presence and absence of two motor-deficit-inducing drugs: tolperisone and harmaline. Rapid acquisition and rapid extinction patterns of ICSS responding were observed in the head-dipping and place-learning paradigms. In contrast to these pre-drug similarities in responding, dramatic differences were noted after drug administration. Tolperisone significantly reduced head-dipping but not place-learning ICSS responding. Similarly, reduction of ICSS responding after harmaline was more pronounced in the head-dipping task. Therefore, the place-learning paradigm may be superior for the assessment of reward values under motor-deficit-inducing conditions in C57BL/6 mice. The relative benefits and disadvantages of both ICSS paradigms are discussed. Combinations of complementary ICSS paradigms using mice may be useful for further investigations of the molecular bases of reward.