NMDA glutamate receptor role in the development of context-dependent and independent sensitization of the induction of stereotypy by amphetamine or apomorphine.

We have been studying sensitization of psychostimulant-induced stereotyped behavior in mice using both a context-dependent and a context-independent paradigm. In the present study, we tested whether N-methyl-D-aspartate (NMDA) receptor antagonists prevent development of sensitization in either of these models. Male CF-1 mice were pretreated with 20 mg/kg (+)3-(2-carboxypiperazine-4yl)-propyl-1-phosphonic acid (CPP), 0.1 mg/kg (+)5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohopten-5, 10-imine maleate (MK-801, dizocilpine maleate), or 25 mg/kg 7-nitroindazole 30 min before a single dose (context-dependent paradigm) or each of three daily doses (context-independent paradigm) of 14 mg/kg amphetamine or 40 mg/kg apomorphine. Two days following this pretreatment, mice were injected with 7 mg/kg amphetamine or 3 mg/kg apomorphine. The stereotyped behavioral response was enhanced in mice pretreated with amphetamine or apomorphine alone, indicating that sensitization had developed. Both CPP and MK-801 prevented the development of sensitization in the context-dependent model but not in the context-independent paradigm. 7-Nitroindazole did not attenuate development of sensitization in either model. The results suggest that activation of glutamatergic receptors is important in some sensitization paradigms but not others, indicating that glutamate can be important but is not always required for the development of sensitization.