Tuberomammillary nucleus lidocaine injections are not rewarding in the conditioned place preference paradigm but are anxiolytic in the elevated plus maze.

摘要

Attenuation of histamine (HA) receptor activation facilitates avoidance learning, but this effect may be a consequence of HA influence on other behavioural systems. The purpose of the present study is to assess the effects of attenuated HA activity on reward and anxiety in rats. The H₁ receptor antagonist diphenhydramine (DP) and bilateral injections of the local anesthetic lidocaine into the tuberomammillary nucleus (TM), the sole source of HA neurons, were tested for rewarding properties using the conditioned place preference (CPP) paradigm. TM lidocaine injections were also tested for effects on anxiety using the elevated plus maze (EPM) paradigm. Although DP (37.8 mg/kg i.p.) produced a CPP, TM lidocaine injections (20 μg/0.5 μl/side) did not. TM lidocaine injections increased time spent on, and frequency of entries onto, the open arms of the EPM, indicating that the drug reduced anxiety. The same injections did not affect enclosed arm entries, a measure of locomotor activity. Our studies demonstrate that, although administration of an H ₁ receptor antagonist is rewarding, inactivation of HA neurons is not. Thus, H₁ receptor antagonizing drugs may be rewarding due to an action on other neurotransmitter systems. Furthermore, because TM lidocaine injections are anxiolytic, the rewarding effect of H₁ antagonists may be influenced by reductions in anxiety.