17β-estradiol locally increases phasic dopamine release in the dorsal striatum

Studies using in vivo microdialysis have shown that 17β-estradiol (E2) increases dopamine (DA) transmission in the dorsal striatum. Both systemic administration of E2 and local infusion into the dorsal striatum rapidly enhance amphetamine-induced DA release. However, it is not known to what degree these effects reflect tonic and/or phasic DA release. It was hypothesized that E2 acts directly within the DS to rapidly increase phasic DA transmission. In urethane-anaesthetized (1.5 mL/kg) female rats, we used fast-scan cyclic voltammetry to study the effects of E2 on phasic, electrically-evoked release of DA in the dorsal striatum. Rats were ovariectomized and implanted with a silastic tube containing 5% E2 in cholesterol, previously shown to mimic low physiological serum concentrations of ∼ 20–25 pg/ml. DA release was evoked every 1 min by delivering biphasic electrical stimulation in the substantia nigra. Local infusions of E2 (244.8 pg/μl) into the dorsal striatum increased the amplitude of the electrically evoked DA transients. Behaviorally significant stimuli and events trigger phasic release of DA. The present findings predict that E2 would boost such signaling in behaving subjects

Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum

The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 vs. 90â 100 s promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5 and 90 s produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 s. We measured cocaine concentrations in the dorsal striatum using rapidâ sampling microdialysis (1 sample/min) and highâ performance liquid chromatographyâ tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of nonâ dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5â s infusions. We also assessed psychomotor activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5â s infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations, and psychomotor activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive.Varying the rate of i.v. cocaine delivery between 5 and 90 s determines the drug’s effects on brain and behaviour. We show that injecting cocaine between 5 and 90 s in rats alters the rates of rise of cocaine and dopamine in the dorsal striatum, without significantly changing peak concentrations. Faster injections also increase locomotor behaviour earlier than slower injections. Thus, beyond achieved dose, differences in the rates of rise of cocaine and dopamine can determine outcome.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/1/ejn13941-sup-0002-reviewer-Comments.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/2/ejn13941.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/3/ejn13941-sup-0001-FigS1-S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151808/4/ejn13941_am.pd

Dataset for: Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum

The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 versus 90-100 seconds promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5-90 seconds produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely-moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 seconds. We measured cocaine concentrations in the dorsal striatum using rapid-sampling microdialysis (1 sample/minute) and high-performance liquid chromatography-tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of non-dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5-second infusions. We also assessed psychomotor activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5-second infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations and psychomotor activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive

MinogianisDataFiles.xlsx

<p><a>The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 versus 90-100 seconds promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain.</a> <a>Here, we predicted that varying the rate of intravenous cocaine infusion between 5-90 seconds produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely-moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 seconds. </a><a>We measured cocaine concentrations in the dorsal striatum using rapid-sampling microdialysis (1 sample/minute) and high-performance liquid chromatography-tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of non-dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5-second infusions. </a><a>We also assessed psychomotor activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5-second infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations and psychomotor activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive.</a></p