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The effects of ceftriaxone on cue-primed reinstatement of cocaine-seeking in male and female rats: estrous cycle effects on behavior and protein expression in the nucleus accumbens.
Psychopharmacology (Berl) 2018; 235(3):837-848P

Abstract

RATIONALE

Effective pharmacological treatments to prevent cocaine relapse remain elusive. In male rats, ceftriaxone attenuates the reinstatement of cocaine-seeking while increasing glutamate transporter-1 (GLT-1) and xCT expression in the nucleus accumbens core (NAc). Despite reported sex differences in cocaine relapse, these effects have not yet been confirmed in female rats.

OBJECTIVE

We investigated the effects of ceftriaxone on cue-primed reinstatement and cocaine-induced alterations in glutamatergic proteins in the NAc of female rats. Potential interactions between estrous phase and treatment were also assessed.

METHOD

Male and female rats self-administered cocaine in the presence of discrete cues for 12 days, followed by 2-3 weeks of extinction. Ceftriaxone or vehicle was administered daily for a minimum of 6 days immediately preceding a cue-primed reinstatement test.

RESULTS

Total cocaine intake was greater in females than in males, but reinstatement behavior was similar. Ceftriaxone attenuated reinstatement in both sexes and was accompanied by increased expression of GLT-1a and xCT in the NAc. However, ceftriaxone attenuated reinstatement only when females were tested during met-, di-, and proestrus phases and not during estrus. A significant increase in AMPA receptor subunit GluA1 surface expression was also observed during estrus, potentially influencing reinstatement.

CONCLUSION

These findings extend the beneficial effects of ceftriaxone on persistent cocaine-seeking from males to females, increasing its potential as a pharmacological treatment for preventing relapse. The effects of estrus on GluA1 expression and reinstatement observed here indicate that females may need additional interventions during some phases of the menstrual cycle.

Authors+Show Affiliations

Department of Psychology, University of Florida, 114 Psychology, 945 Center Dr, Gainesville, FL, 32611-2250, USA. abechard@ufl.edu.Department of Psychology, University of Florida, 114 Psychology, 945 Center Dr, Gainesville, FL, 32611-2250, USA.Department of Psychology, University of Florida, 114 Psychology, 945 Center Dr, Gainesville, FL, 32611-2250, USA. Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.Department of Psychology, University of Florida, 114 Psychology, 945 Center Dr, Gainesville, FL, 32611-2250, USA. Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29197981

Citation

Bechard, Allison R., et al. "The Effects of Ceftriaxone On Cue-primed Reinstatement of Cocaine-seeking in Male and Female Rats: Estrous Cycle Effects On Behavior and Protein Expression in the Nucleus Accumbens." Psychopharmacology, vol. 235, no. 3, 2018, pp. 837-848.
Bechard AR, Hamor PU, Schwendt M, et al. The effects of ceftriaxone on cue-primed reinstatement of cocaine-seeking in male and female rats: estrous cycle effects on behavior and protein expression in the nucleus accumbens. Psychopharmacology (Berl). 2018;235(3):837-848.
Bechard, A. R., Hamor, P. U., Schwendt, M., & Knackstedt, L. A. (2018). The effects of ceftriaxone on cue-primed reinstatement of cocaine-seeking in male and female rats: estrous cycle effects on behavior and protein expression in the nucleus accumbens. Psychopharmacology, 235(3), pp. 837-848. doi:10.1007/s00213-017-4802-7.
Bechard AR, et al. The Effects of Ceftriaxone On Cue-primed Reinstatement of Cocaine-seeking in Male and Female Rats: Estrous Cycle Effects On Behavior and Protein Expression in the Nucleus Accumbens. Psychopharmacology (Berl). 2018;235(3):837-848. PubMed PMID: 29197981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of ceftriaxone on cue-primed reinstatement of cocaine-seeking in male and female rats: estrous cycle effects on behavior and protein expression in the nucleus accumbens. AU - Bechard,Allison R, AU - Hamor,Peter U, AU - Schwendt,Marek, AU - Knackstedt,Lori A, Y1 - 2017/12/02/ PY - 2017/07/25/received PY - 2017/11/26/accepted PY - 2017/12/5/pubmed PY - 2017/12/5/medline PY - 2017/12/4/entrez KW - GLT-1 KW - GluA1 KW - GluA2 KW - mGlu5 KW - xCT SP - 837 EP - 848 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 235 IS - 3 N2 - RATIONALE: Effective pharmacological treatments to prevent cocaine relapse remain elusive. In male rats, ceftriaxone attenuates the reinstatement of cocaine-seeking while increasing glutamate transporter-1 (GLT-1) and xCT expression in the nucleus accumbens core (NAc). Despite reported sex differences in cocaine relapse, these effects have not yet been confirmed in female rats. OBJECTIVE: We investigated the effects of ceftriaxone on cue-primed reinstatement and cocaine-induced alterations in glutamatergic proteins in the NAc of female rats. Potential interactions between estrous phase and treatment were also assessed. METHOD: Male and female rats self-administered cocaine in the presence of discrete cues for 12 days, followed by 2-3 weeks of extinction. Ceftriaxone or vehicle was administered daily for a minimum of 6 days immediately preceding a cue-primed reinstatement test. RESULTS: Total cocaine intake was greater in females than in males, but reinstatement behavior was similar. Ceftriaxone attenuated reinstatement in both sexes and was accompanied by increased expression of GLT-1a and xCT in the NAc. However, ceftriaxone attenuated reinstatement only when females were tested during met-, di-, and proestrus phases and not during estrus. A significant increase in AMPA receptor subunit GluA1 surface expression was also observed during estrus, potentially influencing reinstatement. CONCLUSION: These findings extend the beneficial effects of ceftriaxone on persistent cocaine-seeking from males to females, increasing its potential as a pharmacological treatment for preventing relapse. The effects of estrus on GluA1 expression and reinstatement observed here indicate that females may need additional interventions during some phases of the menstrual cycle. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/29197981/The_effects_of_ceftriaxone_on_cue_primed_reinstatement_of_cocaine_seeking_in_male_and_female_rats:_estrous_cycle_effects_on_behavior_and_protein_expression_in_the_nucleus_accumbens_ L2 - https://dx.doi.org/10.1007/s00213-017-4802-7 DB - PRIME DP - Unbound Medicine ER -