Blockade of behavioral sensitization by MK-801: fact or artifact?

Abstract

The studies reviewed herein have produced results both consistent with and in contradiction to the view that MK-801 and related drugs block behavioral plasticity, and the debate about how exactly MK-801 and related drugs interact with other drugs in sensitization experiments is still in full swing. What seems crucial for future studies relating to this subject is a careful experimental design to reduce the number of potential interpretations of the findings.

The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization

“…However, this conclusion is still highly controversial and the role of NMDARs in addiction remains unclear [78]. The problems with using MK801, including its non-specific side effects and paradoxical ability to induce sensitization to itself, have been reviewed extensively [34][35][36]. It has been repeatedly suggested that alternative antagonists, particularly competitive antagonists, be used in place of MK801.…”

“…Although these studies suggest a role for NMDARs in behavioral sensitization and conditioned place preference, such findings are difficult to interpret because of several serious side effects associated with MK801 administration [34][35][36]. MK801 acts within the NMDA calcium channel in a manner similar to phencyclidine (PCP) and ketamine, and can produce psychosis [37], catalepsy, analgesia, and locomotor hyperactivity.…”

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

“…One possible mechanism by which MK-801 may exert its effect on conditioned responding is that N-methyl-D-aspartate receptor activation may be necessary for retrieval of the neural representation of a nicotine cue. Another possible explanation is that the co-administration of MK-801 with nicotine may create a drug state that is different from that in which the nicotine-sucrose association was learned (see Tzschentke and Schmidt, 2000; see also Wolf, 1998). For this latter possibility, MK-801 has served as an effective discriminative stimulus in operant drug discrimination work (Corbett, 1995, Smith et al, 1999and Zajaczkowski et al, 1996, and therefore, in our study, the addition of MK-801 to nicotine may be creating a distinct cue different from that of nicotine alone.…”

Low doses of dizocilpine block the development and subsequent expression of locomotor sensitization to nicotine in rats

“…However, this effect may occur, not because the NMDA antagonist disrupted the development of sensitization, but because sensitization that may have occurred to the NMDA antagonist/drug combination cannot be retrieved or expressed in the drug alone state (e.g. Tzschentke and Schmidt 2000). For example, Carlezon et al (1995) found that co-administration of 0.3 mg/kg dizocilpine along with the direct dopamine agonist bromocriptine during ten sensitization sessions reduced the subsequent expression of sensitization to a challenge injection of bromocriptine alone, as expected.…”