Acute slices

In acute slices, a mixed response, which consists of fast a7-like and slow components, has been described in interneurons of the stratum oriens (36%of all interneurons). The slow response is sensitive to mecamylamine (I/aM) and to a certain extent to dihydro-/3-erythroi-dine (100 nM), but resistant to the o 3j32 antagonist a-conotoxinMII (200nM). In its moderate sensitivity to dihydro-jS-erythroidine, this response may resemble more o 3j34-like responses (type III) than o 4j82 type II responses (218), although it has been suggested... 

Because of their strategic localization, astrocytes play a crucial role in maintaining the extracellular ionic homeostasis, provide energetic metabolites to neurons and remove excess of neurotransmitter in schedule with synaptic activity. In addition, the strategic location of astrocytes allows them to carefully monitor and control the level of synaptic activity. Indeed, number of papers during the last 15 years have shown that cultured astrocytes can respond to a variety of neurotransmitters with a variety of different patterns of intracellular calcium increases (Verkhratsky et al. 1998). Later on, studies performed in intact tissue preparations (acute brain slices) further established that the plasma membrane receptors can sense external inputs (such as the spillover of neurotransmitters during intense synaptic activity) and transduce them as intracellular calcium elevations, mostly via release of calcium from internal stores (Dani et al. 1992 Murphy et al. 1993 Porter and McCarthy... 

These approaches to receptor identification and classification were, of course, pioneered by studies with peripheral systems and isolated tissues. They are more difficult to apply to the CNS, especially in in vivo experiments, where responses depend on a complex set of interacting systems and the actual drug concentration at the receptors of interest is rarely known. However, the development of in vitro preparations (acute brain slices, organotypic brain slice cultures, tissue-cultured neurons and acutely dissociated neuronal and glial cell preparations) has allowed more quantitative pharmacological techniques to be applied to the action of drugs at neurotransmitter receptors while the development of new recording methods such as patch-clamp... 

I also have another question. When you compare release data from a slice preparation where it is in one application with discrimination data, are you comparing a creature that has received hundreds of injections every other day, on the average 1 do not know what your protocol looks like, but 1 presume every other day is a drug and every other day is a control condition. Here you have an acute preparation and the relationship, of course, is quite tenuous. 

In order to circumvent the difficulties of maintaining known, constant dmg concentrations in the brain in vivo, the hippocampal slice preparation was adapted to study the acute anatomic effects of psychotropic dmgs. This method was implemented in conjunction with Drs. K. Stratton and... 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

Cameron OG, Smith CB Comparison of acute and chronic lithium treatment on 3H-norepinephrine uptake by rat brain slices. Psychopharmacology 67 81-85, 1980... 

External Ca2+ entry, leading to the increase of [Ca2+] , has been reported to occur after electrical (MacVicar el al., 1991) or chemical (Jensen and Chiu, 1991) depolarization of cultured astrocytes, as well as after KC1 depolarization of astrocytes in situ utilizing acute brain slices (Porter and McCarthy, 1995). Accordingly, astrocytes express membrane ion channels, including voltage-sensitive Na+ and K+ channels as well as VSCCs, which may represent the molecular substrate of this aptitude (Barres et al., 1990 Verkhratsky and Steinhauser, 2000). 

An even higher degree of colocalization has been reported in studies using confocal microscopy to detect immunofluorescence for D1 and D2 receptors. These studies have found both types of receptors in virtually all striatal neurons. In cell cultures, D1 and D2 receptors have been colocalized to terminals of intrinsic neurons (Wong et al., 1999). Similarly, Aizman et al. (2000) found that cultured striatal neurons expressed both D1 and D2 receptors. These results are not peculiar to the culture situation. When examined in acutely prepared slices, virtually all cells were positive for both the D1 and D2 subclasses. 

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