Biological Research on Drug Dependence

(I) Studies on neuropeptides, neurohormones and steroids in relation to opioid sensitivity and chronic pain (including animal experimental models, in vitro cell cultures and clinical studies). In clinical studies the project directs to assessment of genetic polymorphism in various transmitter systems combined with quantification of neuropeptide levels in various body fluids. Peptides chosen for analysis includes the tachykinins and opioid peptides. In animal studies models for nociceptive, neuropathic pain are chosen.

(II) Studies on neuropeptides, neurohormones and steroids (in particular anabolic androgenic steroids = AAS) in relation to drug dependence (including experimental animal models, in vitro cell cultures and clinical studies). In clinical studies the project directs to assessment of genetic polymorphism in various transmitter systems combined with quantification of neuropeptide levels in various body fluids. Peptides chosen for analysis includes the tachykinins and opioid peptides. In animal studies models to investigate opiate tolerance and withdrawal and drug self-administration (in collaboration with other laboratories) are used. Endogenous peptides with high potency to attenuate withdrawal reactions have been identified and serve as basis for design and synthesis of peptides and non-peptides that may be further developed to act as drugs in the treatment of opiate addiction. In studies of effects of AAS on the brain neurochemical technologies (radioimmunoassays, autoradiograhy, Western blot, etc.) are combined with various behavioral assays.

(III) Studies on the functions of growth hormone (GH) and prolactin (PRL) and their receptors in the central nervous system (including experimental animal models, in vitro cell cultures and clinical studies). Receptors for GH have been identified in the brain in areas of relevance for many of the known effects of GH on the central nervous system (CNS). Beneficial effects of GH on cognitive functions are recorded by the assessment of memory and cognition using the Water maze in conjunction with various neurobiological techniques.

(IV) Studies on atypical opioid peptides (endomorphins, hemorphins and casomorphins) in relation to behaviour and mechanisms for their release.

(V) Studies on synthetic compounds acting on angiotensin receptors. Receptor assays specific for the AT1, AT2 and AT4 receptors are used to guide synthesis and design of peptide and non-peptide analogues. Compounds with high affinity and selectivity are further studied with regard to agonist activity in functional assay in vitro or in vivo.

Principal investigator: Mathias Hallberg (Fred Nyberg)