S A Sealey | PubMed Health

PubMed1999

Endogenous GABA release is reduced in the striatum of cocaine-sensitized rats.

The magnitude of behavioral sensitization to cocaine is correlated with decreased striatal GABA(A) receptor function. We examined whether GABA release from striatal slices is also altered in cocaine-treated rats. Behavioral sensitization was measured in rats receiving either saline or cocaine (15 mg kg(-1)) daily for 14 days. Cocaine-treated rats showed a significant increase in locomotion and stereotypy over days. Potassium-stimulated endogenous GABA release was measured from superfused striatal slices of these rats. GABA release was significantly decreased in cocaine-treated rats. However, striatal slices preloaded with [(3)H]GABA exhibited a slight but significant increase in release after cocaine sensitization. Similar treatment with a nonsensitizing dose of cocaine (7.5 mg kg(-1)) did not change endogenous GABA release. Saline- and cocaine-treated rats showed no differences in striatal glutamic acid decarboxylase activity at either a saturating or K(m) concentration of glutamate. Therefore, the decrease in endogenous GABA release is not due to a decrease in GABA synthesis, but may reflect changes in GABA storage pools. These data are consistent with an overall decrease in GABA transmission, both pre- and postsynaptically, in the striatum of sensitized rats, which could contribute to enhanced striatal output and behavioral sensitization.

Animals↗

PubMed1997

Simultaneous cocaine exposure abolishes ethanol tolerance.

We measured changes in locomotor impairment in rats caused by ethanol exposure either given alone or simultaneously with cocaine. An initial ethanol injection (2.1 g/kg, intraperitoneally (i.p.) disrupted rotorod performance and this disruption was not significantly affected by the cocaine injection (15 mg/kg, i.p.). After 13 daily drug treatments, performance in the ethanol group was significantly improved whereas in the cocaine+ethanol group, performance remained disrupted to the same extent throughout testing (49 +/- 14 min). Cocaine sensitization developed after repeated exposure and this sensitization was greater in the cocaine+ethanol group. Next, all groups were tested with simultaneous ethanol and cocaine. Tolerance was not diminished in the ethanol group, whereas groups receiving saline, cocaine, or cocaine+ethanol exhibited equally disrupted behavior. During an ethanol-only test, the cocaine+ethanol group also did not respond differently from groups receiving saline or cocaine alone. There was no difference in tolerance of the GABAA receptor to ethanol enhancement in cortical microsacs from the ethanol and cocaine+ethanol groups, nor did cocaine affect blood ethanol levels after initial or repeated exposure. A non-sensitizing dose of cocaine (7.5 mg/kg, i.p.) had no effect on the development or expression of ethanol tolerance. Cocaine disruption of ethanol tolerance thus appears to be partly due to interference of expression of ethanol tolerance by cocaine sensitization and partly due to inhibition of the development of ethanol tolerance by non-GABAergic mechanisms.

Animals↗