A prior history of binge-drinking increases sensitivity to the motivational valence of methamphetamine in female C57BL/6J mice

Abstract

Methamphetamine (MA) and alcohol use disorders exhibit a high degree of co-morbidity and sequential alcohol-MA mixing increases risk for co-abuse. Recently, we reported greater MA-conditioned reward in male C57BL/6J mice with a prior history of binge alcohol-drinking (14 days of 2-hour access to 5, 10, 20 and 40% alcohol). As female mice tend to binge-drink more alcohol than males and females tend to be more sensitive than males to the psychomotor-activating properties of MA, we first characterized the effects of binge-drinking upon MA-induced place-conditioning (four pairings of 0.25, 0.5, 1, 2, or 4 mg/kg IP) in females and then incorporated our prior data to analyze for sex differences in MA-conditioned reward. Prior binge-drinking history did not significantly affect locomotor hyperactivity or its sensitization in female mice. However, the dose-response function for place-conditioning was shifted to the left of water-drinking controls, indicating an increase in sensitivity to MA-conditioned reward. The examination of sex differences revealed no sex differences in alcohol intake, although females exhibited greater MA-induced locomotor stimulation than males, irrespective of their prior drinking history. No statistically significant sex difference was apparent for the potentiation of MA-conditioned reward produced by prior binge-drinking history. If relevant to humans, these data argue that both males and females with a prior binge-drinking history are similarly vulnerable to MA abuse and it remains to be determined whether or not the neural substrates underpinning this increased vulnerability reflect common or sex-specific adaptations in reward-related brain regions.

ERK-Directed Phosphorylation of mGlu5 Gates Methamphetamine Reward and Reinforcement in Mouse

“…Based on our prior studies of alcohol-CPP in Grm5 AA/AA mice [ 47 ], the BNST may play a key role in MA-CPP/CPA. Alternatively, accumulating evidence indicates a cross-sensitization between the rewarding properties of alcohol and MA [ 49 , 65 , 66 ] that we theorize reflects common glutamate-related neuroadaptations within the nucleus accumbens (see Ref. [ 26 ] for discussion).…”

“…Each place-conditioning session was 15 min in duration, and throughout conditioning and testing, the total distance traveled was also recorded to examine for off-target effects of U0126 infusion and genotypic differences in MA-induced psychomotor activation and sensitization [ 26 , 27 , 28 , 48 , 50 , 65 , 66 , 71 , 72 ].…”

Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains

“…Consistent with the limited literature comparing alcohol intake between B6 mice from the Jackson lineage versus the NIH lineage [ 57 , 58 , 59 , 60 , 61 ], alcohol intake under our 3-bottle, 2 h, DID procedure was greater in B6J versus B6NJ mice, with a similar (albeit less robust) substrain difference observed under a more traditional single-bottle DID procedure [ 77 ]. Although blood ethanol concentrations (BECs) could not be determined in Experiment 1 (see Methods), the levels of alcohol intake exhibited by B6NJ and B6J mice are predicted, based on our published data using this model [ 76 , 78 , 79 , 80 ] and those of others employing single-bottle DID procedures e.g., [ 77 , 81 ] to result in BECs below and above, respectively, the 80 mg/dL criterion for binge drinking [ 82 ]. Aligning with this position, although the alcohol intake was lower overall under the single- versus multi-bottle DID procedures employed in the present study, the overall average BEC attained under the single-bottle procedure was above the NIAAA criterion for binge drinking.…”

“…A33 pretreatment occurred 30 min prior to behavioral testing and was administered intraperitoneally (IP) at an injection volume of 10 mL/kg. As we [ 76 ] have demonstrated that mice tend to binge-drink more alcohol when offered a choice between various concentrations versus a single concentration alone, ethyl alcohol (190 proof) was diluted with potable tap water for consumption to final concentrations of 10%, 20% and 40% ( v / v ) for Experiment 1 as in recent binge-drinking studies by our group [ 78 , 79 , 80 ]. To determine whether or not the A33-induced reduction in alcohol intake under multi-bottle DID procedures generalizes to a more traditional single-bottle DID procedure, ethyl alcohol (190 proof) was diluted in potable water to a final concentration of 20% ( v / v ) [ 28 , 88 , 89 , 90 , 91 ].…”

“…Experiment 1 employed a 3-bottle DID procedure that we have shown repeatedly engenders consistently high alcohol intake (≥4.5 g/kg in 2 h) and high blood ethanol concentrations (BECs ≥ 80 mg/dL) in B6J isogenic and congenic mice [ 76 , 78 , 79 , 80 ]. Moreover, this multi-bottle-choice procedure enables an examination of A33 effects upon the dose–response function for alcohol binge drinking, important for conclusions regarding the potential psychopharmacological mechanisms through which A33 exerts its effects upon alcohol intake that are not afforded under the more traditional single-bottle DID procedure [ 28 , 77 ].…”