Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine

Abstract

We examined the effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptor, on the development and expression of behavioral sensitization to amphetamine and cocaine in rats. A single injection of NBQX (12.5 mg/kg) administered 30 min prior to cocaine during the induction phase (days 1-5) prevented the development of cocaine sensitization, assessed by responsiveness to cocaine challenge on day 8. This NBQX regimen did not affect development of amphetamine sensitization. Two pretreatment injections of NBQX, one 20 min before and one 70 min after amphetamine on each day of the induction phase (days 1-6), did not affect sensitization of stereotypy but prevented sensitization of post-stereotypy ambulatory hyperactivity (both assessed by responsiveness to amphetamine challenge on day 8). The effect of NBQX on ambulatory sensitization was dose-dependent (attenuation with 12.5 mg/kg, complete prevention with 25 mg/kg). In contrast to its effects on development, NBQX (25 mg/kg) did not prevent expression of sensitization to cocaine or amphetamine. NBQX itself exerted no significant effects on locomotor activity in either drug-naive rats or rats that had received either NBQX or amphetamine repeatedly. These findings support a requirement for AMPA receptor stimulation in the development of locomotor sensitization to cocaine and amphetamine, but suggest a different mechanism for sensitization of amphetamine stereotypy.

Previous Exposure to Psychostimulants Enhances the Reinstatement of Cocaine Seeking by Nucleus Accumbens AMPA

“…Infusing AMPA into the NAcc produces enhanced locomotion in rats exposed to cocaine 2-3 weeks earlier (Bell and Kalivas, 1996;Pierce et al, 1996a) and AMPA receptor antagonists prevent the expression of locomotor sensitization by amphetamine (Karler et al, 1991;Tzschentke and Schmidt, 1997;Mead and Stephens, 1998;cf, Li et al, 1997) and cocaine (Pierce et al, 1996a;Jackson et al, 1998;Bell et al, 2000;cf, Karler et al, 1994;Li et al, 1997). The present results are consistent with these findings and extend them to the reinstatement of drug seeking.…”

“…For example, infusions of AMPA into the NAcc produce enhanced locomotion in animals exposed to cocaine 2-3 weeks earlier (Bell and Kalivas, 1996;Pierce et al, 1996a) and AMPA receptor antagonists administered systemically (Karler et al, 1991;Tzschentke and Schmidt, 1997;Jackson et al, 1998;Mead and Stephens, 1998;cf, Karler et al, 1994;Li et al, 1997) or into the NAcc (Pierce et al, 1996a;Bell et al, 2000) prevent the expression of locomotor sensitization by amphetamine (AMPH) and cocaine. When taken in light of the above findings and others showing that sensitization enhances the pursuit and self-administration of drugs (Vezina, 2004), these results suggest that previous exposure to psychostimulants should enhance the ability of NAcc AMPA to reinstate drug seeking.…”

The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders

“…Interestingly, emerging animal behavioral studies also suggest that facilitating AMPA receptor throughput may be associated with antidepressant-like effects, whereas attenuating it results in antimanic-like effects (as assessed by stimulant-induced hyperactivity and measures of hedonic activityFcardinal symptoms of the manic syndrome) (Choi et al, 2005;Kaddis et al, 1995;Li et al, 1997;Ossowska et al, 2004;Vanover, 1998). Several classes of compounds can allosterically modulate AMPA receptors.…”

Previous Exposure to VTA Amphetamine Enhances Cocaine Self-Administration under a Progressive Ratio Schedule in an NMDA, AMPA/Kainate, and Metabotropic Glutamate Receptor-Dependent Manner

“…The systemic administration of either NMDA (Karler et al, 1989;Wolf et al, 1995) or AMPA/kainate (Karler et al, 1991a;Li et al, 1997;cf Akiyama et al, 1998) receptor antagonists as well as the application into the VTA of either NMDA (Cador et al, 1999;Vezina and Queen, 2000) or mGlu (Kim and Vezina, 1998) receptor antagonists has been shown to prevent the induction of AMPH-induced locomotor sensitization. Moreover, systemically administering NMDA receptor antagonists with AMPH during preexposure also prevents cellular correlates of locomotor Figure 6 Injection cannula tip placements in the VTA.…”

“…Indeed, induction of locomotor sensitization by AMPH has been shown to be dependent on activation of Nmethyl-D-aspartate (NMDA: Cador et al, 1999;Vezina and Queen, 2000) and metabotropic glutamate (mGlu: Kim and Vezina, 1998) receptors in the VTA. Systemic administration of NMDA (Karler et al, 1989;Wolf et al, 1995) or a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptor antagonists (Karler et al, 1991a;Li et al, 1997) also prevents the development of locomotor sensitization by systemic AMPH. Moreover, induction of locomotor sensitization by AMPH is blocked by lesions of the PFC, which provides major glutamatergic afferentation to the VTA Cador et al, 1999).…”