Cocaine behavioral sensitization and the excitatory amino acids

Abstract

Studies were conducted to identify neuroeffector systems involved in behavioral sensitization to cocaine-induced stereotypy in mice, and to compare the results with those from our previous amphetamine studies. The effects of eight relatively selective neuroeffector agonists and antagonists were measured in mice in order to identify specific functional changes associated with the sensitization. In contrast to amphetamine, the only neuroeffector response altered by cocaine sensitization was a decrease in convulsive threshold to kainate. The persistence of the change in convulsive threshold correlated with the persistence of behavioral sensitization. The induction of sensitization was blocked by pretreatment with four different classes of drugs, represented by haloperidol, dizocilpine, diltiazem and DNQX. These results suggest that the mechanism of induction to cocaine is similar to that of amphetamine; both the glutamate and dopaminergic systems appear to be involved in induction. The expression of the sensitized cocaine response was blocked by haloperidol, CPP and diltiazem. These results differed from those obtained previously insofar as CPP did not affect the expression of sensitization to amphetamine. Furthermore, DNQX, in contrast to its antagonism of the expression of amphetamine sensitization, did not affect the expression of cocaine sensitization. The pharmacological data suggest that the mechanism of induction differs from that of expression, and that the mechanism of expression for cocaine sensitization differs from that for amphetamine.

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

“…Co-administration of MK801 prevents the development of sensitization to cocaine [15][16][17][18][19][20][21][22][23], amphetamine [24][25][26][27][28] and methamphetamine [29,30]. Moreover, MK801 similarly prevents the development of cocaine, amphetamine, and methamphetamineinduced conditioned place preference, a prominent associative memory model of drug seeking behavior [31][32][33].…”

“…It has been accepted that NMDARs are critical for the development of cocaine-induced sensitization. This notion is primarily based on evidence that co-administration of MK801 with cocaine completely blocks [15][16][17][18][19][20][21][22][23] or reduces [16,33,49,76,77] cocaine-induced sensitization. However, this conclusion is still highly controversial and the role of NMDARs in addiction remains unclear [78].…”

Critical Role for Ventral Tegmental Glutamate in Preference for a Cocaine-Conditioned Environment

“…Previous studies showed that systemic administration of glutamate antagonists blocked cocaine-induced locomotor sensitization (Wolf and Jeziorski, 1993;Karler et al, 1994), acquisition of self-administration (Schenk et al, 1993) and conditioned place preference (Cervo and Samanin, 1995;Kim et al, 1996). In addition, intra-VTA injections of NMDA antagonists have been reported to block locomotor sensitization to both cocaine (Kalivas and Alesdatter, 1993) and amphetamine (Cador et al, 1999).…”

“…Previous work has shown that peripheral or intra-VTA administration of glutamate antagonists is rewarding (Steinpreis et al, 1995;David et al, 1998;Panos et al, 1999) and can increase the rewarding properties of established cocaine reinforcement (Ranaldi et al, 1996;Pierce et al, 1997). Similar treatments, however, have also been shown to block learning reinforced by psychostimulants (Schenk et al, 1993;Cervo and Samanin, 1996;Kim et al, 1996) and to attenuate locomotor sensitization to psychostimulants (Kalivas and Alesdatter, 1993;Wolf and Jeziorski, 1993;Karler et al, 1994;Kim et al, 1996;Cornish et al, 2001). These findings indicate that glutamate antagonists do not alter the learning of cocaine reward because they are aversive (in fact they are rewarding), or because they decrease cocaine reward (they actually increase it if it has already been established).…”

Expression of Amphetamine-Induced Behavioral Sensitization after Short- and Long-Term Withdrawal Periods: Participation of μ- and δ-Opioid Receptors

“…Glutamate receptor antagonists, as well as excitotoxic lesions of the prefrontal cortex (PFC), can block the development of behavioral sensitization to psychostimulants (Karler et al, 1989(Karler et al, , 1994Wolf and Khansa, 1991;Kalivas and Alesdatter, 1993;Schenk et al, 1993;Stewart and Druhan, 1993;Wolf and Jeziorski, 1993;Ohmori et al, 1994;Wolf et al, 1995;Cador et al, 1999). Moreover, release of glutamate in the NAc and VTA is enhanced in amphetamine-sensitized rats (Xue et al, 1996;Wolf andXue, 1998, 1999;Wolf et al, 2000).…”