Psychopharmacology and Addiction Biology

In March 2025, the Valdman Institute of Pharmacology at Pavlov First Saint Petersburg State Medical University marked its 30th anniversary. The Institute was founded to integrate educational, methodological, and research activities. In 1996, it was named in honor of Academician Valdman who made an outstanding contribution to the development of Russian pharmacology.

The scientific traditions of the Institute stem from a distinguished lineage of pharmacologists at the University. Established by the Institute’s founder, V.K. von Anrep—the pioneer of local anesthesia—these traditions were further advanced in the works of Likhachev, Zakusov, and Valdman, who laid the foundations of modern pain pharmacology and psychopharmacology.

Over the past 30 years, the Institute has conducted large-scale research in neuropharmacology, investigating a broad spectrum of pharmacological targets, including opioid, nicotinic, and glutamatergic receptors. In addition to fundamental experimental research, the Institute’s staff have carried out clinical studies that led to the registration in Russia of such medicinal products as Bupranal^® (buprenorphine) and Buprakson^® (buprenorphine + naloxone), among others.

The Institute of Pharmacology comprises six laboratories conducting research in the following key areas:

• pain research: development and optimization of treatment strategies for pain syndromes, including migraine and visceral pain;
• psychopharmacology and addictology: investigation of the mechanisms of addiction and behavioral disorders; identification and preclinical evaluation of novel anti-addictive and psychotropic agents; development of industry standards for assessing addictive potential;
• behavioral pharmacology: study of cognitive functions, including cognitive flexibility, and the role of trace amine-associated receptors in affective and anxiety disorders.

The Institute of Pharmacology actively collaborates with leading Russian and international research centers and is a member of reputable international professional societies. It regularly hosts major scientific conferences, including those with international participation, and makes a substantial contribution to the training of scientific personnel, continuing to advance the rich traditions of Russian pharmacological science.

Depression represents a global medical and social challenge, necessitating improvements in treatment effectiveness. One of the key therapeutic challenges is the pronounced interindividual variability in response to antidepressants. This narrative review summarizes current evidence on the role of the gut microbiota in shaping interindividual differences in antidepressant treatment effectiveness. A comparative analysis of pharmacokinetic mechanisms (effects on drug absorption, metabolism, bioaccumulation, and blood–brain barrier permeability) and pharmacodynamic mechanisms (modulation of neurotransmitter systems, neuroplasticity, and neuroinflammation) is presented. Bidirectional interactions between antidepressants and the gut microbial community are also discussed. The available data indicate that although the microbiota functions as an active pharmacokinetic filter, its influence on pharmacodynamics appears to play a decisive role in determining variability in therapeutic response. Even when adequate drug delivery is achieved, intestinal dysbiosis may create an unfavorable pathophysiological milieu that impairs the functional state of central nervous system targets, primarily through suppression of neuroplasticity and induction of inflammation. This conclusion shifts the focus of future research from identifying pharmacokinetic predictors of response to investigating the microbiota-induced pharmacodynamic context. The development of personalized microbiome-modulating adjunctive interventions based on assessment of the functional state of the gut–brain axis appears to be a promising strategy for improving the effectiveness of antidepressant therapy.

BACKGROUND: Consumption of large amounts of alcohol within a short period of time (binge drinking) among adolescents is considered a risk factor for the development of various disorders, including cognitive impairment, the underlying mechanisms of which remain insufficiently understood.

AIM: The work aimed to investigate the delayed effect of alcohol exposure during adolescence on brain mRNA expression of neuronal synuclein proteins, dysfunction of which may represent a key factor in dopaminergic impairment and the pathogenesis of cognitive disorders in adulthood.

METHODS: mRNA expression was assessed by quantitative real-time reverse transcription polymerase chain reaction in samples of the midbrain, striatum, amygdala, and hypothalamus obtained from adult (postnatal day 58) male Wistar rats that had received injections of 20% ethanol solution (intraperitoneally at dose of 3 g/kg, once daily) from postnatal day 30 to 40.

RESULTS: Increased α-synuclein mRNA levels were observed in the striatum and midbrain of animals exposed to alcohol during adolescence. mRNA expression of genes functionally associated with α-synuclein was analyzed, including vesicular proteins of the SNARE (Soluble NSF Attachment Protein Receptor) complex—SNAP-25 (Synaptosomal-Associated Protein of 25 kDa) and VAMP2 (Vesicle-Associated Membrane Protein 2)—as well as dopamine-related genes. Rats exposed to alcohol during adolescence demonstrated elevated tyrosine hydroxylase mRNA levels compared with controls (p = 0.019). In contrast, mRNA levels of γ-synuclein, SNAP-25, VAMP2, dopamine receptor subtype 2, and the dopamine transporter remained unchanged.

CONCLUSION: Alcohol intoxication during adolescence results in increased mRNA expression of α-synuclein and tyrosine hydroxylase in the midbrain of adult animals. These changes likely underlie long-term alterations in dopaminergic neurotransmission and may contribute to brain and behavioral dysfunction.

BACKGROUND: Unpredictable environmental changes exert stressogenic effects and influence oscillatory processes in living organisms. Antidepressants of various classes possess a chronotropic component in their pharmacological activity; however, their use is associated with a number of adverse effects.

AIM: To investigate the chronotropic effects of synthetic analogs of the C-terminal fragment of arginine vasopressin in comparison with fluoxetine by assessing the structure of active swimming in the Porsolt test.

METHODS: The chronopharmacological properties of synthetic analogs of the C-terminal fragment of arginine vasopressin were studied using the forced swim test (Porsolt test). Sexually mature male Wistar rats (n = 89) were placed in a water cylinder twice for 16 minutes. During the second exposure, the number of active swimming episodes with harmonics of < 6 s, 6–18 s, and >18 s was recorded. Experimental procedures were conducted during the autumn–winter period (September to January) from 13:00 to 15:30 under artificial lighting (fluorescent lamp SL 36/26-735). Synthetic analogs of the C-terminal fragment of arginine vasopressin, N-Ac-DSer-Pro-DArg-Gly-NH₂ and N-Ac-Trp-Pro-Arg-Gly-NH₂, were administered intranasally at doses of 0.1, 1.0, and 10.0 μg/kg; fluoxetine was administered intraperitoneally at a dose of 20 mg/kg.

RESULTS: The most favorable effect on the temporal trends of active swimming in the forced swim test was observed with the tetrapeptide N-Ac-Trp-Pro-Arg-Gly-NH₂ at a dose of 1.0 μg/kg. Its effect was similar to that of fluoxetine, demonstrating a significant increase in the number of active swimming episodes lasting >18 s compared with the stressed control group. In addition, peptide administration resulted in a significant increase in the number of swimming cycles lasting 6–18 s, an effect not observed with the standard antidepressant.

CONCLUSION: N-Ac-Trp-Pro-Arg-Gly-NH₂ at a dose of 1.0 μg/kg improves adaptive processes under forced swim stress conditions and appears promising for further investigation of its pharmacological properties.

This year marks the 120th anniversary of the birth of the outstanding Soviet scientist, Doctor of Chemical Sciences, Professor, and Corresponding Member of the Academy of Medical Sciences of the USSR, Nikolai V. Khromov-Borisov.

The principal focus of N.V. Khromov-Borisov’s scientific work was the investigation of the structure of the cholinergic receptor using pharmacochemical approaches. His studies of the relationship between spatial molecular structure and curare-like activity, as well as the influence of the distance between cationic groups on molecular activity, enabled him, together with M.Ya. Michelson, to formulate the hypothesis of the tetrameric structure of the cholinergic receptor. It should be emphasized that this work was carried out in the mid-1960s, when molecular biological methods were not yet sufficiently developed to isolate and study receptor proteins and complexes. In subsequent years, new research techniques refined the understanding of cholinergic receptor structure and established the precise site of action of bis-cationic compounds. Nevertheless, the tetrameric model proposed by N.V. Khromov-Borisov and M.Ya. Michelson significantly facilitated the rational design of muscle relaxants and contributed to the development of both short-acting and long-acting agents. His application of quantum chemistry and molecular mechanics to conformational studies of biologically active molecules and to the determination of three-dimensional pharmacophore structures allows N.V. Khromov-Borisov to be regarded as an outstanding chemist. His work laid the foundation for molecular drug design.

A brilliant chemist involved in the development of numerous medicinal products, an excellent educator whom students regarded as one of the finest lecturers of the First Leningrad Medical Institute, and a broadly educated and creatively gifted individual—all of these descriptions aptly characterize Nikolai V. Khromov-Borisov.