Electrolytic microinfusion transducer system: an alternative method of intracranial drug application

doi:10.1016/0165-0270(80)90016-3

Journal of Neuroscience Methods

Volume 2, Issue 3, June 1980, Pages 273-275

https://doi.org/10.1016/0165-0270(80)90016-3 Get rights and content

Abstract

An intracranial microinfusion system is described which can reliably deliver nl vols. of drug in freely moving animals. By the elimination of the flexible tubing and fluid swivel used in most microinjection systems, the usual unreliability of drug delivery is reduced. Since this system does not require the use of a fluid swivel, simultaneous application of drug to multiple brain sites is possible.

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Cited by (57)

Selective breeding for high alcohol preference is associated with increased sensitivity to cannabinoid reward within the nucleus accumbens shell
2020, Pharmacology Biochemistry and Behavior
Citation Excerpt :
Details can be found in previous publications (e.g., Rodd-Henricks et al., 2002; Hauser et al., 2014). An electrolytic microinfusion transducer (EMIT) system (see Bozarth and Wise, 1980) was used to control microinfusions of drug or vehicle (Rodd-Henricks et al., 2002; Hauser et al., 2014). Depression of the active lever delivered the infusion current for 5 s, which led to the rapid generation of H2 gas and raised the pressure inside the airtight cylinder, in turn, forcing 100-nl of infusate through the injection cannula.
The rate of cannabinoid intake by those with alcohol use disorder (AUD) exceeds that of the general public. The high prevalence of co-abuse of alcohol and cannabis has been postulated to be predicated upon both a common predisposing genetic factor and the interaction of the drugs within the organism. The current experiments examined the effects of cannabinoids in an animal model of AUD.
The present study assessed the reinforcing properties of a cannabinoid receptor 1 (CB1) agonist self-administered directly into the nucleus accumbens shell (AcbSh) in female Wistar and alcohol-preferring (P) rats.
Following guide cannulae surgery aimed at AcbSh, subjects were placed in an operant box equipped with an ‘active lever’ (fixed ratio 1; FR1) that caused the delivery of the infusate and an ‘inactive lever’ that did not. Subjects were arbitrarily assigned to one of seven groups that self-administered either artificial cerebrospinal fluid (aCSF), or 3.125, 6.25, 12.5, or 25 pmol/100 nl of O-1057, a water-soluble CB1 agonist, dissolved in aCSF. The first four sessions of acquisition are followed by aCSF only infusates in sessions 5 and 6 during extinction, and finally the acquisition dose of infusate during session 7 as reinstatement.
The CB1 agonist was self-administered directly into the AcbSh. P rats self-administered the CB1 agonist at lower concentrations and at higher rates compared to Wistar rats.
Overall, the data indicate selective breeding for high alcohol preference has produced rats divergent in response to cannabinoids within the brain reward pathway. The data support the hypothesis that there can be common genetic factors influencing drug addiction.
Alcohol-preferring (P) rats are more sensitive than Wistar rats to the reinforcing effects of cocaine self-administered directly into the nucleus accumbens shell
2011, Pharmacology Biochemistry and Behavior
Citation Excerpt :
Testing was conducted in standard two-lever operant chambers as previously described (Ikemoto et al., 1997b; Rodd-Henricks et al., 2002; Rodd et al., 2005). The electrolytic microinfusion transducer (EMIT) system has also been described in detail (Bozarth and Wise, 1980). For testing, subjects were brought to the testing room, the stylet was removed, and the injection cannula screwed into place.
Wistar rats will self-administer cocaine directly into the nucleus accumbens shell (AcbSh), but not into the nucleus accumbens core. In human and animal literature, there is a genetic association between alcoholism and cocaine dependency. The current experiment examined whether selective breeding for high alcohol preference is also associated with greater sensitivity of the AcbSh to the reinforcing properties of cocaine. P and Wistar rats were given cocaine (0, 100, 200, 400, or 800 pmol/100 nl) to self-infuse into the AcbSh. Rats were given cocaine for the first 4 sessions (acquisition), artificial CSF for sessions 5 and 6 (extinction), and cocaine again in session 7 (reinstatement). During acquisition, P rats self-infused 200–800 pmol cocaine (59 infusions/session), whereas Wistar rats only reliably self-infused 800 pmol cocaine (38 infusions/session). Furthermore, P rats received a greater number of cocaine infusions in the 200, 400 and 800 pmol cocaine groups compared to respective Wistar groups during acquisition. Both P and Wistar rats reduced responding on the active lever when aCSF was substituted for cocaine, and reinstated responding in session 7 when cocaine was restored. However, P rats had significantly greater infusions during session 7 compared to session 4 at all concentrations of cocaine tested, whereas Wistar rats only displayed greater infusions during session 7 compared to session 4 at the 400 and 800 pmol cocaine concentrations. The present results suggest that, compared to Wistar rats, the AcbSh of P rats was more sensitive to the reinforcing effects of cocaine. The reinstatement data suggest that the AcbSh of P rats may have become sensitized to the reinforcing effects of cocaine. Overall, the findings from this study support a genetic association between high alcohol preference and greater sensitivity to the reinforcing effects of cocaine.
Stress-free microinjections in conscious rats
2011, Journal of Neuroscience Methods
Citation Excerpt :
Although it was possible to insert a microinjector without waking up sleeping rat (data not shown), this procedure was laborious and prone to failure due to the fragility of long pieces of fused silica tubing, so we chose not to use this technique. Another approach called electrolytic microinfusion was developed to the point that commercial versions were available (Bozarth and Wise, 1980; Goeders et al., 1984). We have no personal experience with that approach, but practical problems have been reported by others (Hesse et al., 1997).
Microinjections are a major tool in modern neuroscience. Microinjection techniques in conscious animals typically involve four steps: (1) animal adapts to experimental setup; (2) injection system is filled and the microinjector is carefully inserted; (3) a drug solution is injected; (4) 1–2 min later the microinjector is carefully removed. Steps 2 and 4 are difficult to perform in rodents without disturbing the animal. This disruption can cause stress and accompanying tachycardia and hyperthermia – unwanted artifacts in physiological research. To reduce these effects, we altered the traditional approach. Our procedure of microinjection consisted of the following steps: (1) we filled the injection setup and fixed the microinjector in its guide cannula; (2) allowed an animal to adapt to the setup; (3) performed an experiment including microinjection(s); (4) removed the microinjector after the experiment was complete. The key change we incorporated was a 1 m long piece of tubing with a small internal diameter; it allowed us to inject nanoliter volumes through the injector which had been placed into the guide cannula in advance. This way we avoided the usual manipulations related to microinjection, and minimized extraneous disturbances to the rat. In this report we describe the details of this technique in conscious rats and provide examples of the effects and the reproducibility of a 100 nL drug injection on cardiovascular function.
A flexible system for hands-free intracranial microinjection
2009, Journal of Neuroscience Methods
Neuroscience research projects often use intracranial (IC) microinfusions to target drug delivery to specific brain areas during behavioral testing. These experiments require accurate and precisely-timed delivery of small volumes. We present here a stepper motor-powered micropump assembly for such delivery. This system is hands-free, does not use a potentially leaky fluid swivel or use long delivery tubes that are subject to peristaltic forces during animal movements, and has been applied in combination with other paradigms. This micropump system reliably delivers a wide range of fluid volumes (e.g. 50 nL to 1 μL in tissue or greater for intraventricular injections) bilaterally from two independent, commercially available microsyringes through standard surgically implanted guide cannulae. It is easy to build and disassemble for cleaning or changing microsyringes. This system can also be used for a variety of purposes, e.g. intracranial self-administration, place conditioning, and many more, with the advantage that it provides a way to gather important data in the seconds and minutes following IC microinfusion without disruption of the animal's behavior by handling.
Mapping of chemical trigger zones for reward
2004, Neuropharmacology
Addictive drugs are thought to activate brain circuitry that normally mediates more natural rewards such as food or water. Drugs activate this circuitry at synaptic junctions within the brain; identifying the junctions at which this occurs provides clues to the neurochemical and anatomical characteristics of the circuitry. One approach to identifying the junctions at which drugs interact with this circuitry is to determine if animals will lever-press for site-specific microinjections of addictive drugs. This approach has identified GABAergic, dopaminergic, glutamatergic, and cholinergic trigger zones within meso-corticolimbic circuitry important for natural reward function.
The reinforcing effects of acetaldehyde in the posterior ventral tegmental area of alcohol-preferring rats
2002, Pharmacology Biochemistry and Behavior
Acetaldehyde (ACD), the first metabolite of ethanol, is a biologically active compound, which may mediate some of the reinforcing, behavioral and neurotoxic effects of ethanol. The objective of this study was to test the hypothesis that ACD is reinforcing within the mesolimbic system. The intracranial self-administration (ICSA) technique was employed to determine whether ACD was reinforcing in the posterior ventral tegmental area (VTA), a site that supports the reinforcing actions of ethanol. Adult female alcohol-preferring (P) rats were implanted with guide cannulae aimed at the posterior VTA. Subjects were placed in two-lever operant chambers 7–10 days after surgery. Responding on the “active lever” on a fixed ratio 1 (FR1) schedule of reinforcement caused the delivery of 100 nl of infusate, whereas responses on the “inactive lever” were without consequences. Rats were assigned to one of five groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout all eight sessions (4 h in duration) or 3- and 6-, 11- and 23-, 45- and 90- or 180- and 360-μM ACD for the eight sessions, with the lower concentration of ACD given for the initial four sessions and the higher concentration of ACD given for the last four sessions. A second experiment examined the acquisition (first four sessions), extinction (aCSF in sessions 5 and 6) and reinstatement using 90-μM ACD. A third experiment examined the effects of extending the time-out period (from 5 to 55 s) on the number and pattern of infusions of 23-μM ACD. Adult P rats readily self-administered 6–90-μM ACD and discriminated between the active and inactive levers. Furthermore, rats self-administering 90-μM ACD also demonstrated extinction behavior when aCSF was substituted for ACD and gradually reinstated active lever responding when ACD was reintroduced. P rats maintained similar numbers of infusions and infusion patterns under both time-out schedules. Overall, the data indicate that ACD is a potent reinforcer within the posterior VTA of the P rat.

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Research paperElectrolytic microinfusion transducer system: an alternative method of intracranial drug application

Abstract

Pharmacol. Biochem. Behav.

Brain Res. Bull.

Research paper
Electrolytic microinfusion transducer system: an alternative method of intracranial drug application