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Application of a protein synthesis inhibitor into the ventral tegmental area, but not the nucleus accumbens, prevents behavioral sensitization to cocaine.
Synapse. 1995 Jul; 20(3):217-24.S

Abstract

Recent evidence implicates a crucial role for the ventral tegmental area (VTA) in the initiation of behavioral sensitization produced by repeated psychostimulant exposure, while changes in the nucleus accumbens (NAcc) are not critical during the initiation stage. We investigated whether the development of behavioral sensitization to repeated daily cocaine could be prevented by daily administration of the protein synthesis inhibitor, anisomycin, delivered onto VTA neurons. Rats were given five daily treatments as follows: obturators containing crystalline anisomycin or no compound (sham) were placed directly into the VTA 15 min prior to a saline (1 ml/kg, i.p.) or cocaine (15 mg/kg, i.p.) injection. After withdrawal for 8-9 days, the locomotor response to the same dose of saline or cocaine was monitored. No differences in the locomotor response to an acute saline challenge were found across the four groups. Animals given sham treatments in the VTA and daily cocaine demonstrated a significant augmentation in the locomotor response to a cocaine challenge compared to saline controls. Anisomycin treatments alone produced no effects on acute cocaine-induced locomotion. Further, a cocaine challenge in animals receiving daily anisomycin and cocaine elicited a non-augmented response similar to that of saline controls. Thus, the sensitized locomotor response to a cocaine challenge in daily cocaine pretreated animals was completely blocked by daily anisomycin treatment in the VTA. When daily anisomycin was administered into the NAcc along with daily cocaine, no blockade of behavioral sensitization was observed. These results provide support for a critical role of long-term changes in gene expression in the vicinity of VTA neurons mediating the development of sensitization to psychostimulants.

Authors+Show Affiliations

Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7570353

Citation

Sorg, B A., and C Ulibarri. "Application of a Protein Synthesis Inhibitor Into the Ventral Tegmental Area, but Not the Nucleus Accumbens, Prevents Behavioral Sensitization to Cocaine." Synapse (New York, N.Y.), vol. 20, no. 3, 1995, pp. 217-24.
Sorg BA, Ulibarri C. Application of a protein synthesis inhibitor into the ventral tegmental area, but not the nucleus accumbens, prevents behavioral sensitization to cocaine. Synapse. 1995;20(3):217-24.
Sorg, B. A., & Ulibarri, C. (1995). Application of a protein synthesis inhibitor into the ventral tegmental area, but not the nucleus accumbens, prevents behavioral sensitization to cocaine. Synapse (New York, N.Y.), 20(3), 217-24.
Sorg BA, Ulibarri C. Application of a Protein Synthesis Inhibitor Into the Ventral Tegmental Area, but Not the Nucleus Accumbens, Prevents Behavioral Sensitization to Cocaine. Synapse. 1995;20(3):217-24. PubMed PMID: 7570353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of a protein synthesis inhibitor into the ventral tegmental area, but not the nucleus accumbens, prevents behavioral sensitization to cocaine. AU - Sorg,B A, AU - Ulibarri,C, PY - 1995/7/1/pubmed PY - 1995/7/1/medline PY - 1995/7/1/entrez SP - 217 EP - 24 JF - Synapse (New York, N.Y.) JO - Synapse VL - 20 IS - 3 N2 - Recent evidence implicates a crucial role for the ventral tegmental area (VTA) in the initiation of behavioral sensitization produced by repeated psychostimulant exposure, while changes in the nucleus accumbens (NAcc) are not critical during the initiation stage. We investigated whether the development of behavioral sensitization to repeated daily cocaine could be prevented by daily administration of the protein synthesis inhibitor, anisomycin, delivered onto VTA neurons. Rats were given five daily treatments as follows: obturators containing crystalline anisomycin or no compound (sham) were placed directly into the VTA 15 min prior to a saline (1 ml/kg, i.p.) or cocaine (15 mg/kg, i.p.) injection. After withdrawal for 8-9 days, the locomotor response to the same dose of saline or cocaine was monitored. No differences in the locomotor response to an acute saline challenge were found across the four groups. Animals given sham treatments in the VTA and daily cocaine demonstrated a significant augmentation in the locomotor response to a cocaine challenge compared to saline controls. Anisomycin treatments alone produced no effects on acute cocaine-induced locomotion. Further, a cocaine challenge in animals receiving daily anisomycin and cocaine elicited a non-augmented response similar to that of saline controls. Thus, the sensitized locomotor response to a cocaine challenge in daily cocaine pretreated animals was completely blocked by daily anisomycin treatment in the VTA. When daily anisomycin was administered into the NAcc along with daily cocaine, no blockade of behavioral sensitization was observed. These results provide support for a critical role of long-term changes in gene expression in the vicinity of VTA neurons mediating the development of sensitization to psychostimulants. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/7570353/Application_of_a_protein_synthesis_inhibitor_into_the_ventral_tegmental_area_but_not_the_nucleus_accumbens_prevents_behavioral_sensitization_to_cocaine_ L2 - https://doi.org/10.1002/syn.890200305 DB - PRIME DP - Unbound Medicine ER -