Supplemental Digital Content is Available in the Text.This unique multicenter approach provides high-quality evidence validating burrowing as a robust and reproducible outcome measure to infer the global effect of pain on rodents.

DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) is a selective neurotoxin for the locus coeruleus noradrenergic system in the rodent and bird brain. It readily passes the blood-brain barrier and cyclizes to a reactive aziridinium derivative that is accumulated into the noradrenergic nerve terminals via the noradrenaline transporter. DSP4 is also an irreversible inhibitor of this transporter. Within the nerve terminals the aziridinium derivative reacts with unknown vital cellular components, destroying the terminals. At the dose 50 mg/kg i.p. this is characterized by a rapid and long-lasting loss of noradrenaline and a slower decrease in the dopamine-β-hydroxylase enzyme activity and immunoreactivity in the regions innervated from locus coeruleus. The tissue level of noradrenaline is reduced to 10-30% of the normal value. The extraneuronal concentration is, on the other hand, increased due to inflow from non-lesioned regions. Like the peripheral sympathetic nerves the non-locus coeruleus noradrenergic systems in the rodent brain is resistant to the neurotoxic action of DSP4. Serotoninergic and dopaminergic nerves are only slightly or not at all affected by DSP4. The neurotoxic effect is counteracted by pretreatment with noradrenaline uptake inhibitors (e.g., desipramine). MAO-B inhibitors of the N-propargylamine type (e.g., selegiline) also counteract the DSP4-induced neurotoxicity with another, yet unknown mechanism. Because of its selectivity for the locus coeruleus system DSP4 is a useful tool in studies of the functional role of this noradrenergic system in the brain.

and 3 Preclinical R&D, Astra Arcus AB, SoÈ dertaÈ lje, Sweden1 The e ects of treating groups of rats with four di erent anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in di erent brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacri®ced 2 days after the ®nal injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The e ect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. 2 The DOPAC+HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was signi®cantly increased only in the methandrostenolone treated group. 3 The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone-and oxymetholone-treated rats, while the 5-HT synthesis rate was not a ected by the AAS-treatments. 4 The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were una ected. The MAO-B activity was not changed. 5 The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems.

The effects of single and repeated electroconvulsive treatments (ECTs) on brain regional distribution of substance P (SP), neurokinin A (NKA), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and galanin (GAL) were studied in the rat. Rats were divided into four groups receiving one of the following treatments: one ECT, one sham ECT, six ECTs, or six sham ECTs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, striatum, occipital cortex, hippocampus, hypothalamus, and pituitary sections. Peptides were extracted by boiling the tissues in 1 mol/l acetic acid and measured in extract aliquots by specific radioimmunoassays. Marked regional differences (P = .0005) were found for each of the peptides measured. The highest concentrations of SP and NKA were found in the hypothalamus and, in descending order, in striatum, pituitary, frontal cortex, occipital cortex, and hippocampus. For NT, the highest level was found in the hypothalamus and, in descending order, in pituitary, striatum, hippocampus, frontal cortex, and occipital cortex. The highest VIP concentrations were measured in frontal and occipital cortex, followed by pituitary, hypothalamus, striatum, and hippocampus. The highest NPY and GAL concentrations were found in the hypothalamus and the pituitary; in frontal and occipital cortex, as well as in the striatum and hippocampus, the peptides levels were rather evenly distributed. Repeated handling (stress?) decreased both NT and GAL in frontal (P = .05 and .04) and occipital cortex (P = .09 and .07). ECT, one or six treatments, had no effect on SP, NKA, NT, VIP, or GAL concentrations in different brain regions. However, an increase in NPY concentrations in hippocampus (six sham ECTs vs.(ABSTRACT TRUNCATED AT 250 WORDS)