Neuropathic pain in aged rats: behavioral responses and astrocytic activation.

We used the Bennett and Xie (1988) model of chronic neuropathic pain to study the effect of age on thermal and tactile sensitivity and on astrocytic activation in the dorsal horn of the spinal cord after nerve injury. Fischer 344 FBNF1 hybrid rats in three age groups, 4-6, 14-16, and 24-26 months, were studied. Rats were either unligated (day 0, control) or the left sciatic nerve was loosely ligated to cause a chronic constriction injury (CCI). CCI causes a neuropathic pain condition characterized by tactile allodynia and thermal hyperalgesia. Rats were behaviorally assessed for tactile and thermal sensitivity of their ligated and unligated hind paws up to 35 days postligation. Rats were sacrificed before or at various days postligation, and activated astrocytes were identified at the L4-L5 levels of their spinal cords by use of an antibody to glial fibrillary acid protein (GFAP). The number of GFAP-ir astrocytes in the dorsal horn of the spinal cord in the control, uninjured condition decreased with age (P < or = 0.001) but increased after CCI in all three age groups. After CCI, astrocytic activation in the cord was less robust in aged rats than in younger ones (P < or = 0.01). Not all the CCI rats displayed hyperalgesia to touch and to heat. Rats with an increased sensitivity to heat had increased levels of GFAP-ir in their cords; however, rats with decreased thermal sensitivity also displayed increased GFAP-ir. Thus the presence of activated astrocytes was not correlated with a single behavioral manifestation of neuropathic pain.

Secure cranial-mount intrathecal cannulation - a spinal administration technique in the rat.

In order to identify an acute spinally mediated pharmacological effect of a bioactive substance, without incurring untoward supraspinal effects, it is necessary to administer the agent locally onto the spinal cord. The procedure delineated herein presents a modern technique to install a stable, permanent indwelling thecal cannulae with a cranially mounted aperture, and details a simple, repeatable administration system. These methods facilitate a quick, noninvasive spinal drug microadministration that is most useful for differentiation of the locus of pharmacological action without the behavioral disruption associated with other administration methodologies.

Genetic selection for nicotine activity in mice correlates with conditioned place preference.

Genetically heterogenous stock (HS) mice are being used to develop lines which have differential locomotor response to subcutaneously administered (0.75 mg/kg) nicotine. These groups of nicotine-depressed, nicotine-activated or randomly bred control mice were tested as to conditioned place preference using the same dose of nicotine employed to determine their locomotor performance in activity tests. Results indicate that the nicotine-activated mice showed a significantly greater preference to nicotine when compared to the nicotine-depressed mice; this effect was seen in the first generation and continued in the more recently tested third generation. Evidence is offered to support the hypothesis that it is the stimulatory effects of drugs (of abuse) that can be directly correlatable with the strength of their reinforcing effect upon behavior.

Direct microinjection of cathinone into the rat brain produces discriminative stimuli.

Rats were trained to discriminate IP administration of 800 micrograms/kg cathinone using a food-motivated, two-lever discrimination procedure. Following training, 800 micrograms/kg cathinone discrimination was produced (generalized) by lower cathinone doses in a dose-responsive manner after IP administration; an ED50 value of 330 micrograms/kg was calculated. Subsequently, guide cannulae were implanted into the lateral ventricle and bilaterally into the nucleus accumbens. After recovery, injections were made via cannulae that extended 0.5 mm past the tip of the guide cannulae. ICV administration of 256 micrograms cathinone/rat produced discriminative responding on the cathinone-appropriate lever to the same degree as did the peripherally administered training dose of cathinone. Decreasing ICV doses produced decreased discriminative performance and allowed the calculation of an ED50 value of 90.5 micrograms. Likewise, administration of 64 micrograms cathinone/nucleus accumbens (for a total of 128 micrograms/rat) substituted for the IP training dose of cathinone. These results evidence the central mediation of the cathinone-induced discriminative stimulus cue and show that administration of cathinone into the nucleus accumbens is sufficient to produce these stimuli. Thus, these data suggest that receptors in the nucleus accumbens are important for the discrimination of this psychostimulant.

A case of obsessive-compulsive disorder related to AIDS: psychopharmacologic treatment.

It is well known that delusions, obsessions and phobic reactions may centre on items which are of current topical interest. We report a case of obsessive-compulsive disorder manifested primarily by intrusive thoughts about AIDS. The patient eventually responded to an unusual combination of medications.