Isoflurane anesthesia interferes with the expression of cocaine-induced sensitization in female rats

Abstract

Repeated cocaine administration results in a progressive sensitization of behavior which typically occurs more readily in female rats than in males. Our recent studies of rats undergoing surgical procedures revealed that following anesthesia, females sensitized less than males receiving identical repeated cocaine injections. Since isoflurane acts primarily by increasing the effects of the inhibitory neurotransmitter γ-amino butyric acid (GABA) and reducing the effects of the excitatory amino acid glutamate, these amino acids may play more prominent roles in sensitization to cocaine in females than previously understood. In order to examine the effects of isoflurane on cocaine sensitization, we administered cocaine (15mg/kg i.p) or saline to adult male and female Sprague-Dawley rats for 9 days; on day 10, half of the rats were subjected to isoflurane anesthesia and the other half did not receive anesthesia. On day 11, rats were given their last dose of either cocaine or saline. We recorded behaviors for 1 hour on days 1, 9 and 11. Locomotor activity and stereotyped behaviors were quantified using photo beam monitors and the scoring of video tapes respectively. Results indicated that a single exposure to isoflurane significantly dampens the stereotypic behavior associated with repeated cocaine administration in females but not in males. They further suggest that either GABA or glutamate play more prominent roles in cocaine-sensitization behavior in females than in males.

Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone

“…While the present results further implicate gonadal hormones and their metabolites in the sex-differences found in addiction research, more work is needed to elucidate the mechanisms driving these differences. In addition to the present findings, past result suggest that investigating neurobiological differences in GABA functions between males and females may be of interest (Campbell et al, 2002; Febo and Segarra, 2004; Siegal and Dow-Edwards, 2009). …”

Effects of gaboxadol on the expression of cocaine sensitization in rats.

“…Then we compared the effects of systemic (Experiment 2) and intracranial (Experiment 3) GBX administration on the expression of cocaine sensitization in male and female rats. We had previously demonstrated that administration of isoflurane, which targets α4βδ GABA A receptors among others (Jia, Pignataro, & Harrison, 2007), dampens cocaine sensitization in rats (Siegal & Dow-Edwards, 2009). We therefore hypothesized that systemic administration of GBX, which is more selective than isoflurane, would affect cocaine sensitization in a similar way.…”

Elective Anesthesia and Surgery in Veteran Patients Abusing Cocaine - Factors Influencing Management Decisions

“…The results of the study suggest that cocaine interferes with intra-neuronal uptake of neuromediators leading to a stepwise increase in the arrhythmogenicity of epinephrine. Other studies in different animal models showed similar effects [23][24][25][26]. About 2% of pregnancy-related DVT develops in the upper limb [25].…”

“…Other studies in different animal models showed similar effects [23][24][25][26]. About 2% of pregnancy-related DVT develops in the upper limb [25]. But the cases of DVT developing in association with reproductive technologies occur predominantly in the upper limb or neck in pregnant patients who had ovarian hyperstimulation syndrome [17].…”