Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: a neurochemical study

Abstract

In addition to dopamine (DA), evidence indicates that glutamatergic regulation of the mesolimbic reward pathway is involved in mediating the abuse-related effects of psychostimulants, including amphetamine. Since rats raised in an enrichment condition (EC) during development are more sensitive to the locomotor stimulant effects of acute amphetamine compared to rats raised in an impoverished condition (IC), the present study examined amphetamine-induced extracellullar glutamate and aspartate levels in the nucleus accumbens (NAcc) of EC and IC rats using in vivo microdialysis coupled with HPLC-electrochemical detection. Basal extracellular levels of glutamate or aspartate were not significantly different between EC and IC rats. Acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) increased extracellular glutamate levels in NAcc of EC rats (137% or 305% of basal) and IC rats (120% or 187% of basal). Similarly, acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) elevated aspartate levels in NAcc of EC rats (148% or 237% of basal) and IC rats (115% or 170% of basal). Glutamate levels were elevated by amphetamine to a greater extent in EC rats than in IC rats. Pretreatment with systemic MK-801 (0.25 mg/kg, ip), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, prevented the acute amphetamine-induced increase in extracellular glutamate and aspartate levels in NAcc. Overall, these results suggest that alterations in glutamate in the NAcc may be involved in the environment-dependent effects of amphetamine.

Fig. 1

Typical locations of microdialysis probe placements in NAcc as indicated by black lines. Numbers to the right indicate distance in mm from bregma according to Paxinos and Watson (1986). The active probe protruded 2 mm below the distal end of the guide cannulae for NAcc as described in methods.

Fig. 2

Time course effect of acute amphetamine (AMPH) given at either 0.5 mg/kg (upper panel) or 2 mg/kg (lower panel) on extracellular glutamate level in NAcc of EC and IC rats. After collection of basal samples, rats were given saline (SAL) injection, as indicated by left arrow (↑) and then samples were collected for 60 min before AMPH injection, right arrow (↑). Data represent the mean ± SEM of 6–7 animals. *p < 0.05, significant difference from IC rats at same sampling time interval.

Fig. 3

Time course effect of acute amphetamine (AMPH) given at either 0.5 mg/kg (upper panel) or 2 mg/kg (lower panel) on extracellular aspartate level in NAcc of EC and IC rats. After collection of basal samples, rats were given saline (SAL) injection, as indicated by left arrow (↑) and then samples were collected for 60 min before AMPH injection, right arrow (↑). Data represent the mean ± SEM of 6–7 animals. *p < 0.05, significant difference from IC rats at same sampling time interval.

Fig. 4

Time course effect of acute amphetamine (AMPH, 2 mg/kg, sc) given in combination with systemic MK-801 (0.25 mg/kg) on extracellular glutamate or aspartate levels in NAcc of EC rats. After collection of basal samples, rats were given saline (SAL) injection as indicated by left arrow (↑) and samples were collected for 40 min, followed by MK-801, as indicated by middle arrow (↑), and 20 min later, followed by AMPH as indicated by right arrow (↑). Data represent the mean ± SEM of 6 animals.